Skip to main content
SpringerLink
Log in

Pathophysiology and Management Approaches for Parkinson’s Disease

  • Chapter
  • First Online:
Drug Delivery Strategies in Neurological Disorders: Challenges and Opportunities

  • 127 Accesses

Abstract

Parkinson’s disease (PD), a most common face of neurodegenerative disorders, affects the aged population worldwide. The disease affects neurological functions causing motor and nonmotor symptoms. The pathophysiology for such a debilitating disorder remains elusive due to the involvement of complex pathological cascades and proteins. The key molecular players remain to be α-synuclein (α-Syn), organelle dysfunction (mitochondria, ER, lysosomes), autophagic failure, and oxidative stress. The conventional therapy has been targeting symptomatic management by replenishing the dopamine levels, but as the pathological markers were explored, the management paradigm has now shifted toward disease-modifying agents. Even nonpharmacological interventions like deep brain stimulation, mitochondrial transplantation, stem cell therapy, etc., have now come into the picture. Besides such interventions, developing alternative drug delivery systems like the nanotechnological approach has grabbed attention in past decades to overcome the limitations of the existing conventional therapy. The major challenge in PD management still remains to be targeted therapy for treatment-resistant patients at later stages of the treatment regime. The pathological marker refinement and appropriation for selecting a best-fit treatment regime for PD patients may be a promising approach for PD management.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aflaki E, Borger DK, Moaven N, Stubblefield BK, Rogers SA, Patnaik S et al (2016) A new glucocerebrosidase chaperone reduces α-synuclein and glycolipid levels in iPSC-derived dopaminergic neurons from patients with Gaucher Disease and Parkinsonism. J Neurosci 36(28):7441–7452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahlskog JE, Muenter MD (2001) Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord. 16(3):448–458

    Article  CAS  PubMed  Google Scholar 

  • Alarcón-Arís D, Recasens A, Galofré M, Carballo-Carbajal I, Zacchi N, Ruiz-Bronchal E et al (2018) Selective α-synuclein knockdown in monoamine neurons by intranasal oligonucleotide delivery: potential therapy for Parkinson’s disease. Mol Ther. 26(2):550–567

    Article  PubMed  Google Scholar 

  • Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 9:357–381

    Article  CAS  PubMed  Google Scholar 

  • Antal A, Herrmann CS (2016) Transcranial alternating current and random noise stimulation: possible mechanisms. Neural Plast. 2016:3616807

    Article  PubMed  PubMed Central  Google Scholar 

  • Ariga H, Takahashi-Niki K, Kato I, Maita H, Niki T, Iguchi-Ariga SMM (2013) Neuroprotective function of DJ-1 in Parkinson’s disease. Oxid Med Cell Longev. 2013:683920

    Article  PubMed  PubMed Central  Google Scholar 

  • Arisoy S, Sayiner O, Comoglu T, Onal D, Atalay O, Pehlivanoglu B (2020) In vitro and in vivo evaluation of levodopa-loaded nanoparticles for nose to brain delivery. Pharm Dev Technol. 25(6):735–747. https://doi.org/10.1080/10837450.2020.1740257

    Article  CAS  PubMed  Google Scholar 

  • Arnulf I, Konofal E, Merino-Andreu M, Houeto JL, Mesnage V, Welter ML et al (2002) Parkinson’s disease and sleepiness: an integral part of PD. Neurology. 58(7):1019–1024

    Article  CAS  PubMed  Google Scholar 

  • Asemi-Rad A, Moafi M, Aliaghaei A, Abbaszadeh H-A, Abdollahifar M-A, Ebrahimi M-J et al (2022) The effect of dopaminergic neuron transplantation and melatonin co-administration on oxidative stress-induced cell death in Parkinson’s disease. Metab Brain Dis. 37(8):2677–2685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baptista MAS, Merchant K, Barrett T, Bhargava S, Bryce DK, Ellis JM et al (2020) LRRK2 inhibitors induce reversible changes in nonhuman primate lungs without measurable pulmonary deficits. Sci Transl Med. 12(540):eaav0820

    Article  CAS  PubMed  Google Scholar 

  • Barzilay R, Ben-Zur T, Bulvik S, Melamed E, Offen D (2009) Lentiviral delivery of LMX1a enhances dopaminergic phenotype in differentiated human bone marrow mesenchymal stem cells. Stem Cells Dev. 18(4):591–601

    Article  CAS  PubMed  Google Scholar 

  • Beavan MS, Schapira AHV (2013) Glucocerebrosidase mutations and the pathogenesis of Parkinson disease. Ann Med. 45(8):511–521

    Article  CAS  PubMed  Google Scholar 

  • Behl T, Kaur I, Kumar A, Mehta V, Zengin G, Arora S (2020) Gene therapy in the management of Parkinson’s disease: potential of GDNF as a promising therapeutic strategy. Curr Gene Ther. 20(3):207–222

    Article  CAS  PubMed  Google Scholar 

  • Ben SD, Kahana N, Kampel V, Warshawsky A, Youdim MBH (2004) Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6-hydroxydopamine lession in rats. Neuropharmacology. 46(2):254–263

    Article  Google Scholar 

  • Bendor JT, Logan TP, Edwards RH (2013) The function of α-synuclein. Neuron. 79(6):1044–1066

    Article  CAS  PubMed  Google Scholar 

  • Benninger DH, Lomarev M, Lopez G, Wassermann EM, Li X, Considine E et al (2010) Transcranial direct current stimulation for the treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry. 81(10):1105–1111

    Article  PubMed  Google Scholar 

  • Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 1(1):11–21

    Article  CAS  PubMed  Google Scholar 

  • Bibbiani F, Oh JD, Kielaite A, Collins MA, Smith C, Chase TN (2005) Combined blockade of AMPA and NMDA glutamate receptors reduces levodopa-induced motor complications in animal models of PD. Exp Neurol. 196(2):422–429

    Article  CAS  PubMed  Google Scholar 

  • Bido S, Muggeo S, Massimino L, Marzi MJ, Giannelli SG, Melacini E et al (2021) Author Correction: Microglia-specific overexpression of α-synuclein leads to severe dopaminergic neurodegeneration by phagocytic exhaustion and oxidative toxicity. Nat Commun. 12:7359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q et al (2014) The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 510(7505):370–375

    Article  CAS  PubMed  Google Scholar 

  • Bocci T, Prenassi M, Arlotti M, Cogiamanian F, Borrellini L, Moro E et al (2021) Eight-hours conventional versus adaptive deep brain stimulation of the subthalamic nucleus in Parkinson’s disease. NPJ Park Dis. 7:88

    Article  CAS  Google Scholar 

  • Boll M-C, Alcaraz-Zubeldia M, Rios C (2011) Medical management of Parkinson’s disease: focus on neuroprotection. Curr Neuropharmacol. 9(2):350–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bologna M, Guerra A, Paparella G, Giordo L, Alunni Fegatelli D, Vestri AR et al (2018) Neurophysiological correlates of bradykinesia in Parkinson’s disease. Brain. 141(8):2432–2444

    Article  PubMed  Google Scholar 

  • Boyd RE, Lee G, Rybczynski P, Benjamin ER, Khanna R, Wustman BA et al (2013) Pharmacological chaperones as therapeutics for lysosomal storage diseases. J Med Chem. 56(7):2705–2725

    Article  CAS  PubMed  Google Scholar 

  • Braak H, Del Tredici K, Rüb U, de Vos RAI, Jansen Steur ENH, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 24(2):197–211

    Article  PubMed  Google Scholar 

  • Brás J, Gibbons E, Guerreiro R (2021) Genetics of synucleins in neurodegenerative diseases. Acta Neuropathol. 141(4):471–490

    Article  PubMed  Google Scholar 

  • Brittain J-S, Probert-Smith P, Aziz TZ, Brown P (2013) Tremor suppression by rhythmic transcranial current stimulation. Curr Biol. 23(5):436–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brodersen P, Voinnet O (2009) Revisiting the principles of microRNA target recognition and mode of action. Nat Rev Mol Cell Biol. 10(2):141–148

    Article  CAS  PubMed  Google Scholar 

  • Brooks DJ, Papapetropoulos S, Vandenhende F, Tomic D, He P, Coppell A et al (2010) An open-label, positron emission tomography study to assess adenosine A2A brain receptor occupancy of vipadenant (BIIB014) at steady-state levels in healthy male volunteers. Clin Neuropharmacol. 33(2):55–60

    Article  CAS  PubMed  Google Scholar 

  • Brotchie JM, Lee J, Venderova K (2005) Levodopa-induced dyskinesia in Parkinson’s disease. J Neural Transm. 112(3):359–391

    Article  CAS  PubMed  Google Scholar 

  • Brunden KR, Lee VM-Y, Smith AB 3rd, Trojanowski JQ, Ballatore C (2017) Altered microtubule dynamics in neurodegenerative disease: Therapeutic potential of microtubule-stabilizing drugs. Neurobiol Dis. 105:328–335

    Article  CAS  PubMed  Google Scholar 

  • Büeler H (2010) Mitochondrial dynamics, cell death and the pathogenesis of Parkinson’s disease. Apoptosis. 15(11):1336–1353

    Article  PubMed  Google Scholar 

  • Cai LJ, Tu L, Li T, Yang XL, Ren YP, Gu R et al (2020) Up-regulation of microRNA-375 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson’s disease by inhibiting SP1. Aging (Albany NY). 12(1):672–689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cankaya S, Cankaya B, Kilic U, Kilic E, Yulug B (2019) The therapeutic role of minocycline in Parkinson’s disease. Drugs Context. 8:212553

    Article  PubMed  PubMed Central  Google Scholar 

  • Carta M, Carlsson T, Kirik D, Björklund A (2007) Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain. 130(Pt 7):1819–1833

    Article  PubMed  Google Scholar 

  • Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T et al (2007) “Rejuvenation” protects neurons in mouse models of Parkinson’s disease. Nature. 447(7148):1081–1086

    Article  CAS  PubMed  Google Scholar 

  • Chaturvedi RK, Beal MF (2008) Mitochondrial approaches for neuroprotection. Ann N Y Acad Sci. 1147:395–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaturvedi RK, Beal MF (2013) Molecular and cellular neuroscience mitochondria targeted therapeutic approaches in Parkinson’s and Huntington’s diseases. Mol Cell Neurosci. 55:101–114

    Article  CAS  PubMed  Google Scholar 

  • Chaugule VK, Burchell L, Barber KR, Sidhu A, Leslie SJ, Shaw GS et al (2011) Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J. 30(14):2853–2867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen K-HS, Chen R (2019) Invasive and noninvasive brain stimulation in Parkinson’s disease: clinical effects and future perspectives. Clin Pharmacol Ther. 106(4):763–775

    Article  PubMed  Google Scholar 

  • Chen J-F, Cunha RA (2020) The belated US FDA approval of the adenosine A(2A) receptor antagonist istradefylline for treatment of Parkinson’s disease. Purinergic Signal. 16(2):167–174

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen T, Li C, Li Y, Yi X, Lee SM-Y, Zheng Y (2016) Oral delivery of a nanocrystal formulation of schisantherin a with improved bioavailability and brain delivery for the treatment of Parkinson’s disease. Mol Pharm. 13(11):3864–3875

    Article  CAS  PubMed  Google Scholar 

  • Cheng G, Liu Y, Ma R, Cheng G, Guan Y, Chen X et al (2022) Anti-Parkinsonian therapy: strategies for crossing the blood-brain barrier and nano-biological effects of nanomaterials. Nano-micro Lett. 14(1):105

    Article  CAS  Google Scholar 

  • Chiu CC, Weng YH, Huang YZ et al (2020) (D620N) VPS35 causes the impairment of Wnt/β-catenin signaling cascade and mitochondrial dysfunction in a PARK17 knockin mouse model. Cell Death Dis 11:1018. https://doi.org/10.1038/s41419-020-03228-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho HJ, Liu G, Jin SM, Parisiadou L, Xie C, Yu J et al (2012) MicroRNA-205 regulates the expression of Parkinson’s disease-related leucine-rich repeat kinase 2 protein. Hum Mol Genet. 22(3):608–620

    Article  PubMed  PubMed Central  Google Scholar 

  • Choi ML, Chappard A, Singh BP, Maclachlan C, Rodrigues M, Fedotova EI et al (2022) Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity. Nat Neurosci. 25(9):1134–1148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cole TA, Zhao H, Collier TJ, Sandoval I, Sortwell CE, Steece-Collier K et al (2021) α-Synuclein antisense oligonucleotides as a disease-modifying therapy for Parkinson’s disease. JCI insight. 6(5):e135633

    Article  PubMed  PubMed Central  Google Scholar 

  • Conn KJ, Gao W, McKee A, Lan MS, Ullman MD, Eisenhauer PB et al (2004) Identification of the protein disulfide isomerase family member PDIp in experimental Parkinson’s disease and Lewy body pathology. Brain Res. 1022(1–2):164–172

    Article  CAS  PubMed  Google Scholar 

  • Cornelissen T, Haddad D, Wauters F, Van Humbeeck C, Mandemakers W, Koentjoro B et al (2014) The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy. Hum Mol Genet. 23(19):5227–5242

    Article  CAS  PubMed  Google Scholar 

  • Cosentino G, Valentino F, Todisco M, Alfonsi E, Davì R, Savettieri G et al (2017) Effects of more-affected vs. less-affected motor cortex tDCS in Parkinson’s disease. Front Hum Neurosci. 11:309

    Article  PubMed  PubMed Central  Google Scholar 

  • Costa G, Abin-Carriquiry JA, Dajas F (2001) Nicotine prevents striatal dopamine loss produced by 6-hydroxydopamine lesion in the substantia nigra. Brain Res. 888(2):336–342

    Article  CAS  PubMed  Google Scholar 

  • Coune PG, Schneider BL, Aebischer P (2012) Parkinson’s disease: Gene therapies. Cold Spring Harb Perspect Med. 2(4):1–15

    Article  Google Scholar 

  • Cunic D, Roshan L, Khan FI, Lozano AM, Lang AE, Chen R (2002) Effects of subthalamic nucleus stimulation on motor cortex excitability in Parkinson’s disease. Neurology. 58(11):1665–1672

    Article  CAS  PubMed  Google Scholar 

  • Daher JPL (2017) Interaction of LRRK2 and $α$-synuclein in Parkinson’s disease. In: Rideout HJ (ed) Leucine-rich repeat kinase 2 (LRRK2). Springer International Publishing, Cham, pp 209–226

    Chapter  Google Scholar 

  • Daher JPL, Abdelmotilib HA, Hu X, Volpicelli-Daley LA, Moehle MS, Fraser KB et al (2015) Leucine-rich repeat kinase 2 (LRRK2) pharmacological inhibition abates α-synuclein gene-induced neurodegeneration. J Biol Chem. 290(32):19433–19444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Miranda BR, Rocha EM, Castro SL, Greenamyre JT (2020) Protection from α-Synuclein induced dopaminergic neurodegeneration by overexpression of the mitochondrial import receptor TOM20. NPJ Park Dis. 6(1):38

    Article  Google Scholar 

  • Deffains M, Bergman H (2019) Parkinsonism-related β oscillations in the primate basal ganglia networks—Recent advances and clinical implications. Parkinsonism Relat Disord. 59:2–8

    Article  PubMed  Google Scholar 

  • Dehay B, Bourdenx M, Gorry P, Przedborski S, Vila M, Hunot S et al (2015) Targeting α-synuclein for treatment of Parkinson’s disease: mechanistic and therapeutic considerations. Lancet Neurol. 14(8):855–866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delgado L, Alfaro I, Valdovinos D, Gomez F, Protter A, Bernales S (2011) P4-164: Dimebon (Latrepirdine) protects from cell death-induced by mitochondrial stressors and alpha-synuclein over-expression, and decreases alpha-synuclein protein levels in a Parkinson’s disease cell model. Alzheimer’s Dement 7(4S\_Part\_22):S760–S761

    Google Scholar 

  • DeMaagd G, Philip A (2015) Parkinson’s disease and its management: part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. P T. 40(8):504–532

    PubMed  PubMed Central  Google Scholar 

  • Deng X, Dzamko N, Prescott A, Davies P, Liu Q, Yang Q et al (2011) Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2. Nat Chem Biol. 7(4):203–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deniston CK, Salogiannis J, Mathea S, Snead DM, Lahiri I, Matyszewski M et al (2020) Structure of LRRK2 in Parkinson’s disease and model for microtubule interaction. Nature. 588(7837):344–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K et al (2006) A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 355(9):896–908

    Article  CAS  PubMed  Google Scholar 

  • Devos D, Moreau C, Devedjian JC, Kluza J, Petrault M, Laloux C et al (2014) Targeting chelatable iron as a therapeutic modality in Parkinson’s disease. Antioxid Redox Signal. 21(2):195–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dexter DT, Statton SA, Whitmore C, Freinbichler W, Weinberger P, Tipton KF et al (2011) Clinically available iron chelators induce neuroprotection in the 6-OHDA model of Parkinson’s disease after peripheral administration. J Neural Transm. 118(2):223–231

    Article  CAS  PubMed  Google Scholar 

  • Dezsi L, Vecsei L (2017) Monoamine oxidase b inhibitors in Parkinson’s disease. CNS Neurol Disord Drug Targets. 16(4):425–439

    Article  CAS  PubMed  Google Scholar 

  • Di Maio R, Barrett PJ, Hoffman EK, Barrett CW, Zharikov A, Borah A et al (2016) α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson’s disease. Sci Transl Med. 8(342):342ra78

    PubMed  PubMed Central  Google Scholar 

  • Du H, Nie S, Chen G, Ma K, Xu Y, Zhang Z et al (2015) Levetiracetam ameliorates L-DOPA-induced dyskinesia in hemiparkinsonian rats inducing critical molecular changes in the striatum. Reichmann H, editor. Parkinson Dis 2015:253878

    Google Scholar 

  • Duncan GW, Firbank MJ, Yarnall AJ, Khoo TK, Brooks DJ, Barker RA et al (2016) Gray and white matter imaging: A biomarker for cognitive impairment in early Parkinson’s disease? Mov Disord. 31(1):103–110

    Article  PubMed  Google Scholar 

  • Durcan TM, Tang MY, Pérusse JR, Dashti EA, Aguileta MA, McLelland G-L et al (2014) USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin. EMBO J. 33(21):2473–2491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eira J, Silva CS, Sousa MM, Liz MA (2016) The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders. Prog Neurobiol. 141:61–82

    Article  CAS  PubMed  Google Scholar 

  • Emin D, Zhang YP, Lobanova E, Miller A, Li X, Xia Z et al (2022) Small soluble α-synuclein aggregates are the toxic species in Parkinson’s disease. Nat Commun. 13(1):5512. https://doi.org/10.1038/s41467-022-33252-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Emre M, Tsolaki M, Bonuccelli U, Destée A, Tolosa E, Kutzelnigg A et al (2010) Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 9(10):969–977

    Article  CAS  PubMed  Google Scholar 

  • Espay AJ, LeWitt PA, Kaufmann H (2014) Norepinephrine deficiency in Parkinson’s disease: The case for noradrenergic enhancement. Mov Disord. 29(14):1710–1719

    Article  CAS  PubMed  Google Scholar 

  • Fanning S, Haque A, Imberdis T, Baru V, Barrasa MI, Nuber S et al (2019) Lipidomic analysis of α-synuclein neurotoxicity identifies stearoyl CoA desaturase as a target for Parkinson treatment. Mol Cell. 73(5):1001–1014.e8

    Article  CAS  PubMed  Google Scholar 

  • Farrell K, Barker RA (2012) Stem cells and regenerative therapies for Parkinson’s disease. Degener Neurol Neuromuscul Dis. 2:79–92

    PubMed  PubMed Central  Google Scholar 

  • Fenoy AJ, Simpson RKJ (2012) Management of device-related wound complications in deep brain stimulation surgery. J Neurosurg. 116(6):1324–1332

    Article  PubMed  Google Scholar 

  • Finkelstein DI, Billings JL, Adlard PA, Ayton S, Sedjahtera A, Masters CL et al (2017) The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson’s disease. Acta Neuropathol Commun. 5(1):53

    Article  PubMed  PubMed Central  Google Scholar 

  • Fox SH, Katzenschlager R, Lim S-Y, Ravina B, Seppi K, Coelho M et al (2011) The movement disorder society evidence-based medicine review update: treatments for the motor symptoms of Parkinson’s disease. Mov Disord. 26(Suppl 3):S2–S41

    PubMed  Google Scholar 

  • Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R et al (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med. 344(10):710–719

    Article  CAS  PubMed  Google Scholar 

  • Fu Y, Zhou L, Li H, Hsiao J-HT, Li B, Tanglay O et al (2022) Adaptive structural changes in the motor cortex and white matter in Parkinson’s disease. Acta Neuropathol. 144:861–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao G, Chen R, He M, Li J, Li J, Wang L et al (2019) Gold nanoclusters for Parkinson’s disease treatment. Biomaterials. 194:36–46

    Article  CAS  PubMed  Google Scholar 

  • Garbayo E, Ansorena E, Blanco-Prieto MJ (2012) Brain drug delivery systems for neurodegenerative disorders. Curr Pharm Biotechnol. 13(12):2388–2402

    Article  CAS  PubMed  Google Scholar 

  • Ge P, Dawson VL, Dawson TM (2020) PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson’s disease. Mol Neurodegener. 15(1):20

    Article  PubMed  PubMed Central  Google Scholar 

  • Giguère N, Burke Nanni S, Trudeau L-E (2018) On cell loss and selective vulnerability of neuronal populations in Parkinson’s disease. Front Neurol. 9:455. https://doi.org/10.3389/fneur.2018.00455

    Article  PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Latapi P, Bhowmick SS, Saranza G, Fox SH (2020) Non-dopaminergic treatments for motor control in Parkinson’s disease: an update. CNS Drugs. 34(10):1025–1044

    Article  CAS  PubMed  Google Scholar 

  • Grégoire L, Samadi P, Graham J, Bédard P, Bartoszyk G, Paolo T (2009) Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-DOPA in parkinsonian monkeys. Parkinsonism Relat Disord. 15:445–452

    Article  PubMed  Google Scholar 

  • Grosso Jasutkar H, Oh SE, Mouradian MM (2022) Therapeutics in the pipeline targeting α-synuclein for Parkinson’s disease. Pharmacol Rev. 74(1):207–237

    Article  PubMed  Google Scholar 

  • Gui Y-X, Xu Z-P, Lv W, Zhao J-J, Hu X-Y (2015) Evidence for polymerase gamma, POLG1 variation in reduced mitochondrial DNA copy number in Parkinson’s disease. Parkinsonism Relat Disord. 21(3):282–286

    Article  PubMed  Google Scholar 

  • Hamadjida A, Nuara SG, Veyres N, Frouni I, Kwan C, Sid-Otmane L et al (2017) The effect of mirtazapine on dopaminergic psychosis and dyskinesia in the parkinsonian marmoset. Psychopharmacology (Berl). 234(6):905–911

    Article  CAS  PubMed  Google Scholar 

  • Han F, Hu B (2020) Stem cell therapy for Parkinson’s disease. Adv Exp Med Biol. 1266:21–38

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa M, Fujiwara H, Nonaka T, Wakabayashi K, Takahashi H, Lee VM-Y et al (2002) Phosphorylated alpha-synuclein is ubiquitinated in alpha-synucleinopathy lesions. J Biol Chem. 277(50):49071–49076

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto M, Masliah E (1999) Alpha-synuclein in Lewy body disease and Alzheimer’s disease. Brain Pathol. 9(4):707–720

    Article  CAS  PubMed  Google Scholar 

  • Hass CJ, Collins MA, Juncos JL (2007) Resistance training with creatine monohydrate improves upper-body strength in patients with Parkinson disease: a randomized trial. Neurorehabil Neural Repair. 21(2):107–115

    Article  PubMed  Google Scholar 

  • Hatcher JM, Zhang J, Choi HG, Ito G, Alessi DR, Gray NS (2015) Discovery of a pyrrolopyrimidine (JH-II-127), a highly potent, selective, and brain penetrant LRRK2 inhibitor. ACS Med Chem Lett. 6(5):584–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hauser RA, Olanow CW, Kieburtz KD, Pourcher E, Docu-Axelerad A, Lew M et al (2014) Tozadenant (SYN115) in patients with Parkinson’s disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol. 13(8):767–776

    Article  CAS  PubMed  Google Scholar 

  • Hayashita-Kinoh H, Yamada M, Yokota T, Yoshikuni M, Mochizuki H (2006) Down-regulation of α-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of Parkinson’s disease rat model. Biochem Biophys Res Commun. 341:1088–1095

    Article  CAS  PubMed  Google Scholar 

  • Healy DG, Falchi M, O’Sullivan SS, Bonifati V, Durr A, Bressman S et al (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study. Lancet Neurol. 7(7):583–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol. 4(11):600–609

    Article  CAS  PubMed  Google Scholar 

  • Henry A, Schapira V (2012) Targeting mitochondria for neuroprotection in Parkinson’s disease. 16:9

    Google Scholar 

  • Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol. 8(4):382–397

    Article  CAS  PubMed  Google Scholar 

  • Hitti FL, Yang AI, Gonzalez-Alegre P, Baltuch GH (2019) Human gene therapy approaches for the treatment of Parkinson’s disease: An overview of current and completed clinical trials. Park Relat Disord. 66:16–24

    Article  Google Scholar 

  • Hoozemans JJM, van Haastert ES, Eikelenboom P, de Vos RAI, Rozemuller JM, Scheper W (2007) Activation of the unfolded protein response in Parkinson’s disease. Biochem Biophys Res Commun. 354(3):707–711

    Article  CAS  PubMed  Google Scholar 

  • Huang R, Ma H, Guo Y, Liu S, Kuang Y, Shao K et al (2013) Angiopep-conjugated nanoparticles for targeted long-term gene therapy of Parkinson’s disease. Pharm Res. 30(10):2549–2559

    Article  CAS  PubMed  Google Scholar 

  • Huot P, Johnston TH, Lewis KD, Koprich JB, Reyes MG, Fox SH et al (2011) Characterization of 3,4-methylenedioxymethamphetamine (MDMA) enantiomers in vitro and in the MPTP-lesioned primate: R-MDMA reduces severity of dyskinesia, whereas S-MDMA extends duration of ON-time. J Neurosci Off J Soc Neurosci. 31(19):7190–7198

    Article  CAS  Google Scholar 

  • Hurley MJ, Dexter DT (2012) Voltage-gated calcium channels and Parkinson’s disease. Pharmacol Ther. 133(3):324–333

    Article  CAS  PubMed  Google Scholar 

  • Ikawa M, Okazawa H, Kudo T, Kuriyama M, Fujibayashi Y, Yoneda M (2011) Evaluation of striatal oxidative stress in patients with Parkinson’s disease using [62Cu]ATSM PET. Nucl Med Biol. 38(7):945–951

    Article  CAS  PubMed  Google Scholar 

  • Ilijic E, Guzman JN, Surmeier DJ (2011) The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson’s disease. Neurobiol Dis. 43(2):364–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaberzadeh S, Bastani A, Zoghi M (2014) Anodal transcranial pulsed current stimulation: A novel technique to enhance corticospinal excitability. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 125(2):344–351

    Article  Google Scholar 

  • Jaberzadeh S, Bastani A, Zoghi M, Morgan P, Fitzgerald P (2015) Anodal transcranial pulsed current stimulation: the effects of pulse duration on corticospinal excitability. PLoS One. 10:e0131779

    Article  PubMed  PubMed Central  Google Scholar 

  • Jenner P, Rocha J-F, Ferreira JJ, Rascol O, Soares-da-Silva P (2021) Redefining the strategy for the use of COMT inhibitors in Parkinson’s disease: the role of opicapone. Expert Rev Neurother. 21(9):1019–1033

    Article  CAS  PubMed  Google Scholar 

  • Jennings D, Huntwork-Rodriguez S, Henry AG, Sasaki JC, Meisner R, Diaz D et al (2022) Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson’s disease. Sci Transl Med. 14(648):eabj2658

    Article  CAS  PubMed  Google Scholar 

  • Jeyarasasingam G, Tompkins L, Quik M (2002) Stimulation of non-alpha7 nicotinic receptors partially protects dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced toxicity in culture. Neuroscience. 109(2):275–285

    Article  CAS  PubMed  Google Scholar 

  • Jin H, Kanthasamy A, Ghosh A, Anantharam V, Kalyanaraman B, Kanthasamy AG (2014) Mitochondria-targeted antioxidants for treatment of Parkinson’s disease: preclinical and clinical outcomes. Biochim Biophys Acta. 1842(8):1282–1294

    Article  CAS  PubMed  Google Scholar 

  • Johnston TH, Fox SH, Piggott MJ, Savola J-M, Brotchie JM (2010) The α2 adrenergic antagonist fipamezole improves quality of levodopa action in Parkinsonian primates. Mov Disord. 25(13):2084–2093

    Article  PubMed  Google Scholar 

  • Johnston TH, Geva M, Steiner L, Orbach A, Papapetropoulos S, Savola J-M et al (2019) Pridopidine, a clinic-ready compound, reduces 3,4-dihydroxyphenylalanine-induced dyskinesia in Parkinsonian macaques. Mov Disord. 34(5):708–716

    Article  CAS  PubMed  Google Scholar 

  • Junghanns S, Glöckler T, Reichmann H (2004) Switching and combining of dopamine agonists. J Neurol. 251 Suppl:VI/19–VI/23

    Google Scholar 

  • Kaufmann H, Nahm K, Purohit D, Wolfe D (2004) Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies. Neurology. 63(6):1093–1095

    Article  PubMed  Google Scholar 

  • Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, Boonplueang R et al (2003) Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson’s disease. Neuron. 37(6):899–909

    Article  CAS  PubMed  Google Scholar 

  • Khatri DK, Preeti K, Tonape S, Bhattacharjee S, Patel M, Shah S, Singh PK, Srivastava S, Gugulothu D, Vora L, Singh SB (2023) Nanotechnological advances for nose to brain delivery of therapeutics to improve the Parkinson therapy. Curr Neuropharmacol 21(3):493–516. https://doi.org/10.2174/1570159X20666220507022701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khoo TK, Yarnall AJ, Duncan GW, Coleman S, O’Brien JT, Brooks DJ et al (2013) The spectrum of nonmotor symptoms in early Parkinson disease. Neurology. 80(3):276–281

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim JS, Kim J-M, Jeong-Ja O, Jeon BS (2010) Inhibition of inducible nitric oxide synthase expression and cell death by (−)-epigallocatechin-3-gallate, a green tea catechin, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. J Clin Neurosci. 17(9):1165–1168

    Article  CAS  PubMed  Google Scholar 

  • Kim D, Yoo JM, Hwang H, Lee J, Lee SH, Yun SP et al (2018) Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease. Nat Nanotechnol. 13(9):812–818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kordower JH, Olanow CW, Dodiya HB, Chu Y, Beach TG, Adler CH et al (2013) Disease duration and the integrity of the nigrostriatal system in Parkinson’s disease. Brain. 136(8):2419–2431. https://doi.org/10.1093/brain/awt192

    Article  PubMed  PubMed Central  Google Scholar 

  • Kulkarni AD, Vanjari YH, Sancheti KH, Belgamwar VS, Surana SJ, Pardeshi CV (2015) Nanotechnology-mediated nose to brain drug delivery for Parkinson’s disease: a mini review. J Drug Target. 23(9):775–788

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Aguirre JD, Condos TEC, Martinez-Torres RJ, Chaugule VK, Toth R et al (2015) Disruption of the autoinhibited state primes the E3 ligase parkin for activation and catalysis. EMBO J. 34(20):2506–2521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kundu P, Das M, Tripathy K, Sahoo SK (2016) Delivery of dual drug loaded lipid based nanoparticles across the blood-brain barrier impart enhanced neuroprotection in a rotenone induced mouse model of Parkinson’s disease. ACS Chem Neurosci. 7(12):1658–1670

    Article  CAS  PubMed  Google Scholar 

  • Kurth MC, Adler CH (1998) COMT inhibition. Neurology. 50(5 Suppl 5):S3:LP-S14

    Google Scholar 

  • Kwon HJ, Kim D, Seo K, Kim YG, Han SI, Kang T et al (2018) Ceria nanoparticle systems for selective scavenging of mitochondrial, intracellular, and extracellular reactive oxygen species in Parkinson’s disease. Angew Chemie Int Ed. 57(30):9408–9412. https://doi.org/10.1002/anie.201805052

    Article  CAS  Google Scholar 

  • Lazarou M, Jin SM, Kane LA, Youle RJ (2012) Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase parkin. Dev Cell. 22(2):320–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lefaucheur J-P, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F et al (2017) Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 128(1):56–92

    Article  Google Scholar 

  • Lehotzky A, Oláh J, Fekete JT, Szénási T, Szabó E, Győrffy B et al (2021) Co-transmission of alpha-synuclein and TPPP/p25 inhibits their proteolytic degradation in human cell models. Front Mol Biosci. 8:666026. https://doi.org/10.3389/fmolb.2021.666026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lesage S, Mangone G, Tesson C, Bertrand H, Benmahdjoub M, Kesraoui S, Arezki M, Singleton A, Corvol J-C, Brice A (2021) Clinical variability of SYNJ1-associated early-onset Parkinsonism. Front Neurol 12:648457. https://doi.org/10.3389/fneur.2021.648457

    Article  PubMed  PubMed Central  Google Scholar 

  • Leveille E, Ross OA, Gan-Or Z (2021) Tau and MAPT genetics in tauopathies and synucleinopathies. Parkinsonism Relat Disord. 90:142–154. https://www.sciencedirect.com/science/article/pii/S1353802021003370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levites Y, Weinreb O, Maor G, Youdim MB, Mandel S (2001) Green tea polyphenol (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. J Neurochem. 78(5):1073–1082

    Article  CAS  PubMed  Google Scholar 

  • Lewitt PA (2008) Levodopa for the treatment of Parkinson’s disease. N Engl J Med. 359(23):2468–2476

    Article  CAS  PubMed  Google Scholar 

  • Lewitt P, Rezai A, Leehey M, Ojemann S, Flaherty A, Eskandar E et al (2011) AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham-surgery controlled. Randomised Trial. Lancet Neurol. 10:309–319

    Article  CAS  PubMed  Google Scholar 

  • Li C, Götz J (2017) Tau-based therapies in neurodegeneration: opportunities and challenges. Nat Rev Drug Discov. 16(12):863–883. https://doi.org/10.1038/nrd.2017.155

    Article  CAS  PubMed  Google Scholar 

  • Li S, Lv X, Zhai K, Xu R, Zhang Y, Zhao S et al (2016) MicroRNA-7 inhibits neuronal apoptosis in a cellular Parkinson’s disease model by targeting Bax and Sirt2. Am J Transl Res. 8(2):993–1004

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li L, Xu J, Wu M, Hu JM (2018) Protective role of microRNA-221 in Parkinson’s disease. Bratisl Lek Listy. 119(1):22–27

    CAS  PubMed  Google Scholar 

  • Lieberman JA 3rd. (2004) Managing anticholinergic side effects. Prim Care Companion J Clin Psychiatry. 6(Suppl 2):20–23

    PubMed  PubMed Central  Google Scholar 

  • Lindvall O (2015) Treatment of Parkinson’s disease using cell transplantation. Philos Trans R Soc B Biol Sci. 370(1680):20140370. https://doi.org/10.1098/rstb.2014.0370

    Article  CAS  Google Scholar 

  • Lindvall O, Brundin P, Widner H, Rehncrona S, Gustavii B, Frackowiak R et al (1990) Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science. 247(4942):574–577

    Article  CAS  PubMed  Google Scholar 

  • Lindvall O, Sawle G, Widner H, Rothwell JC, Björklund A, Brooks D et al (1994) Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson’s disease. Ann Neurol. 35(2):172–180

    Article  CAS  PubMed  Google Scholar 

  • Little S, Pogosyan A, Neal S, Zavala B, Zrinzo L, Hariz M et al (2013) Adaptive deep brain stimulation in advanced Parkinson disease. Ann Neurol. 74(3):449–457

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Q, Zhu D, Jiang P, Tang X, Lang Q, Yu Q et al (2019) Resveratrol synergizes with low doses of L-DOPA to improve MPTP-induced Parkinson disease in mice. Behav Brain Res. 367:10–18

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Liu C, Zhang J, Zhang Y, Liu K, Song J-X et al (2020) A self-assembled α-synuclein nanoscavenger for Parkinson’s disease. ACS Nano. 14(2):1533–1549. https://doi.org/10.1021/acsnano.9b06453

    Article  CAS  PubMed  Google Scholar 

  • Ma L, Liu Y, Zhang S-C (2011) Directed differentiation of dopamine neurons from human pluripotent stem cells. Methods Mol Biol. 767:411–418

    Article  CAS  PubMed  Google Scholar 

  • Madrid J, Benninger DH (2021) Non-invasive brain stimulation for Parkinson’s disease: Clinical evidence, latest concepts and future goals: A systematic review. J Neurosci Methods. 347:108957

    Article  PubMed  Google Scholar 

  • Maiti B, Perlmutter JS (2020) A clinical trial of isradipine: what went wrong? Ann Intern Med. 172(9):625–626

    Article  PubMed  PubMed Central  Google Scholar 

  • Mandler M, Valera E, Rockenstein E, Weninger H, Patrick C, Adame A et al (2014) Next-generation active immunization approach for synucleinopathies: implications for Parkinson’s disease clinical trials. Acta Neuropathol. 127(6):861–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marks WJJ, Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N et al (2010) Gene delivery of AAV2-neurturin for Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol. 9(12):1164–1172

    Article  CAS  PubMed  Google Scholar 

  • Marras C, Beck JC, Bower JH, Roberts E, Ritz B, Ross GW et al (2018) Prevalence of Parkinson’s disease across North America. NPJ Park Dis. 4:21

    Article  CAS  Google Scholar 

  • Masliah E, Rockenstein E, Mante M, Crews L, Spencer B, Adame A et al (2011) Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS One. 6(4):e19338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuse D, Kitada M, Kohama M, Nishikawa K, Makinoshima H, Wakao S et al (2010) Human umbilical cord-derived mesenchymal stromal cells differentiate into functional Schwann cells that sustain peripheral nerve regeneration. J Neuropathol Exp Neurol. 69(9):973–985

    Article  CAS  PubMed  Google Scholar 

  • Mazzulli JR, Zunke F, Tsunemi T, Toker NJ, Jeon S, Burbulla LF et al (2016) Activation of β-glucocerebrosidase reduces pathological α-synuclein and restores lysosomal function in Parkinson’s patient midbrain neurons. J Neurosci Off J Soc Neurosci. 36(29):7693–7706

    Article  CAS  Google Scholar 

  • McCormack AL, Mak SK, Henderson JM, Bumcrot D, Farrer MJ, Di Monte DA (2010) Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra. PLoS One. 5(8):e12122

    Article  PubMed  PubMed Central  Google Scholar 

  • Md S, Khan RA, Mustafa G, Chuttani K, Baboota S, Sahni JK et al (2013) Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: pharmacodynamic, pharmacokinetic and scintigraphy study in mice model. Eur J Pharm Sci 48(3):393–405

    Article  CAS  PubMed  Google Scholar 

  • Mead BP, Kim N, Miller GW, Hodges D, Mastorakos P, Klibanov AL et al (2017) Novel focused ultrasound gene therapy approach noninvasively restores dopaminergic neuron function in a rat Parkinson’s disease model. Nano Lett. 17(6):3533–3542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melzer TR, Watts R, MacAskill MR, Pitcher TL, Livingston L, Keenan RJ et al (2012) Grey matter atrophy in cognitively impaired Parkinson’s disease. J Neurol Neurosurg Psychiatry. 83(2):188–194

    Article  PubMed  Google Scholar 

  • Mezey E, Dehejia AM, Harta G, Tresser N, Suchy SF, Nussbaum RL et al (1998) Alpha synuclein is present in Lewy bodies in sporadic Parkinson’s disease. Mol Psychiatry. 3(6):493–499

    Article  CAS  PubMed  Google Scholar 

  • Migdalska-Richards A, Daly L, Bezard E, Schapira AHV (2016) Ambroxol effects in glucocerebrosidase and α-synuclein transgenic mice. Ann Neurol. 80(5):766–775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller S, Muqit MMK (2019) Therapeutic approaches to enhance PINK1/Parkin mediated mitophagy for the treatment of Parkinson’s disease. Neurosci Lett. 705:7–13

    Article  CAS  PubMed  Google Scholar 

  • Mittal S, Bjørnevik K, Im DS, Flierl A, Dong X, Locascio JJ et al (2017) β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science. 357(6354):891–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moliadze V, Fritzsche G, Antal A (2014) Comparing the efficacy of excitatory transcranial stimulation methods measuring motor evoked potentials. Neural Plast. 2014:837141

    Article  PubMed  PubMed Central  Google Scholar 

  • Monastero R, Baschi R, Nicoletti A, Pilati L, Pagano L, Cicero CE et al (2020) Transcranial random noise stimulation over the primary motor cortex in PD-MCI patients: a crossover, randomized, sham-controlled study. J Neural Transm. 127(12):1589–1597

    Article  PubMed  Google Scholar 

  • Moreau C, Duce JA, Rascol O, Devedjian JC, Berg D, Dexter D et al (2018) Iron as a therapeutic target for Parkinson’s disease. Mov Disord. 33(4):568–574

    Article  PubMed  Google Scholar 

  • Moriyasu S, Shimizu T, Honda M, Ugawa Y, Hanajima R (2022) Motor cortical plasticity and its correlation with motor symptoms in Parkinson’s disease. eNeurologicalSci. 29:100422. https://www.sciencedirect.com/science/article/pii/S2405650222000314

    Article  PubMed  PubMed Central  Google Scholar 

  • Mursaleen L, Somavarapu S, Zariwala MG (2020) Deferoxamine and curcumin loaded nanocarriers protect against rotenone-induced neurotoxicity. J Parkinsons Dis. 10(1):99–111

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa M, Taniguchi Y, Senda S, Takizawa N, Ichisaka T, Asano K et al (2014) A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells. Sci Rep. 4:3594

    Article  PubMed  PubMed Central  Google Scholar 

  • Naren P, Samim KS, Tryphena KP et al (2023) Microtubule acetylation dyshomeostasis in Parkinson’s disease. Transl Neurodegener 12:20. https://doi.org/10.1186/s40035-023-00354-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nash JE, Ravenscroft P, McGuire S, Crossman AR, Menniti FS, Brotchie JM (2004) The NR2B-selective NMDA receptor antagonist CP-101,606 exacerbates L-DOPA-induced dyskinesia and provides mild potentiation of anti-parkinsonian effects of L-DOPA in the MPTP-lesioned marmoset model of Parkinson’s disease. Exp Neurol. 188(2):471–479

    Article  CAS  PubMed  Google Scholar 

  • Nickols HH, Conn PJ (2014) Development of allosteric modulators of GPCRs for treatment of CNS disorders. Neurobiol Dis. 61:55–71

    Article  PubMed  Google Scholar 

  • Ntetsika T, Papathoma PE, Markaki I (2021) Novel targeted therapies for Parkinson’s disease. Mol Med. 27:17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oishi N, Udaka F, Kameyama M, Sawamoto N, Hashikawa K, Fukuyama H (2005) Regional cerebral blood flow in Parkinson disease with nonpsychotic visual hallucinations. Neurology. 65(11):1708–1715

    Article  CAS  PubMed  Google Scholar 

  • Okun MS (2012) Deep-brain stimulation for Parkinson’s disease. N Engl J Med. 367(16):1529–1538

    Article  CAS  PubMed  Google Scholar 

  • Oláh J, Lehotzky A, Szunyogh S, Szénási T, Orosz F, Ovádi J (2020) Microtubule-associated proteins with regulatory functions by day and pathological potency at night. Cells. 9(2):357

    Article  PubMed  PubMed Central  Google Scholar 

  • Ondo WG, Dat Vuong K, Khan H, Atassi F, Kwak C, Jankovic J (2001) Daytime sleepiness and other sleep disorders in Parkinson’s disease. Neurology. 57(8):1392–1396

    Article  CAS  PubMed  Google Scholar 

  • Orr AL, Rutaganira FU, de Roulet D, Huang EJ, Hertz NT, Shokat KM et al (2017) Long-term oral kinetin does not protect against α-synuclein-induced neurodegeneration in rodent models of Parkinson’s disease. Neurochem Int. 109:106–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ou Z, Pan J, Tang S, Duan D, Yu D, Nong H et al (2021) Global trends in the incidence, prevalence, and years lived with disability of Parkinson’s disease in 204 countries/territories from 1990 to 2019. Front public Heal. 9:776847

    Article  Google Scholar 

  • Pal A, Singh A, Nag TC, Chattopadhyay P, Mathur R, Jain S (2013) Iron oxide nanoparticles and magnetic field exposure promote functional recovery by attenuating free radical-induced damage in rats with spinal cord transection. Int J Nanomedicine. 8:2259–2272

    PubMed  PubMed Central  Google Scholar 

  • Pardridge WM (2005) Tyrosine hydroxylase replacement in experimental Parkinson’s disease with transvascular gene therapy. NeuroRx. 2(1):129–138

    Article  PubMed  PubMed Central  Google Scholar 

  • Park H-J, Lee K-W, Park ES, Oh S, Yan R, Zhang J et al (2016) Dysregulation of protein phosphatase 2A in parkinson disease and dementia with lewy bodies. Ann Clin Transl Neurol. 3(10):769–780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park HW, Park CG, Park M, Lee SH, Park HR, Lim J et al (2020) Intrastriatal administration of coenzyme Q10 enhances neuroprotection in a Parkinson’s disease rat model. Sci Rep. 10(1):9572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel AB, Jimenez-Shahed J (2018) Profile of inhaled levodopa and its potential in the treatment of Parkinson’s disease: evidence to date. Neuropsychiatr Dis Treat. 14:2955–2964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel V, Chisholm D, Dua T, Laxminarayan R, Medina-Mora ME, editors. No Title. Washington, DC; 2016.

    Google Scholar 

  • Paton DM (2020) Istradefylline: adenosine A2A receptor antagonist to reduce “OFF” time in Parkinson’s disease. Drugs Today (Barc). 56(2):125–134

    Article  CAS  PubMed  Google Scholar 

  • Pellicano C, Benincasa D, Pisani V, Buttarelli FR, Giovannelli M, Pontieri FE (2007 Feb) Prodromal non-motor symptoms of Parkinson’s disease. Neuropsychiatr Dis Treat. 3(1):145–152

    Article  PubMed  PubMed Central  Google Scholar 

  • Perez CA, Tong Y, Guo M (2008) Iron chelators as potential therapeutic agents for parkinson’s disease. Curr Bioact Compd. 4(3):150–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perez-lloret S, Rascol O (2010) Dopamine receptor agonists for the treatment of early or advanced Parkinson’s disease. CNS Drug 24(11):941–968

    Article  CAS  Google Scholar 

  • Pezzoli G, Zini M (2010) Levodopa in Parkinson’s disease: From the past to the future. Expert Opin Pharmacother. 11(4):627–635

    Article  CAS  PubMed  Google Scholar 

  • Pierantozzi M, Pietroiusti A, Brusa L, Galati S, Stefani A, Lunardi G et al (2006) Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology. 66(12):1824–1829

    Article  CAS  PubMed  Google Scholar 

  • Pinjala P, Tryphena KP, Prasad R, Khatri DK, Sun W, Singh SB, Gugulothu D, Srivastava S, Vora L (2023) CRISPR/Cas9 assisted stem cell therapy in Parkinson’s disease. Abstr Biomater Res 27(1). https://doi.org/10.1186/s40824-023-00381-y

  • Pinto M, Nissanka N, Peralta S, Brambilla R, Diaz F, Moraes CT (2016) Pioglitazone ameliorates the phenotype of a novel Parkinson’s disease mouse model by reducing neuroinflammation. Mol Neurodegener. 11(1):25

    Article  PubMed  PubMed Central  Google Scholar 

  • Popovych OV, Tass PA (2019) Adaptive delivery of continuous and delayed feedback deep brain stimulation—a computational study. Sci Rep. 9(1):10585

    Article  PubMed  PubMed Central  Google Scholar 

  • Potok W, van der Groen O, Bächinger M, Edwards D, Wenderoth N (2022) Transcranial random noise stimulation modulates neural processing of sensory and motor circuits, from potential cellular mechanisms to behavior: A scoping review. eNeuro. 9(1)

    Google Scholar 

  • Prell T (2018) Structural and functional brain patterns of non-motor syndromes in Parkinson’s disease. Front Neurol. 9:138

    Article  PubMed  PubMed Central  Google Scholar 

  • Price DL, Koike MA, Khan A, Wrasidlo W, Rockenstein E, Masliah E et al (2018) The small molecule alpha-synuclein misfolding inhibitor, NPT200-11, produces multiple benefits in an animal model of Parkinson’s disease. Sci Rep. 8(1):16165

    Article  PubMed  PubMed Central  Google Scholar 

  • Priori A, Maiorana N, Dini M, Guidetti M, Marceglia S, Ferrucci R (2021) Adaptive deep brain stimulation (aDBS). Int Rev Neurobiol. 159:111–127

    Article  PubMed  Google Scholar 

  • Radhakrishnan DM, Goyal V (2018) Parkinson’s disease: A review. Neurol India. 66(Supplement):S26–S35

    PubMed  Google Scholar 

  • Randy LH, Guoying B (2007) Agonism of peroxisome proliferator receptor-gamma may have therapeutic potential for neuroinflammation and Parkinson’s disease. Curr Neuropharmacol. 5(1):35–46

    Article  PubMed  PubMed Central  Google Scholar 

  • Ren C, Hu X, Zhou Q (2018) Graphene oxide quantum dots reduce oxidative stress and inhibit neurotoxicity in vitro and in vivo through catalase-like activity and metabolic regulation. Adv Sci. 5(5):1700595. https://doi.org/10.1002/advs.201700595

    Article  CAS  Google Scholar 

  • Rivest J, Barclay CL, Suchowersky O (1999) COMT inhibitors in Parkinson’s disease. Can J Neurol Sci. 26(SUPPL. 2):34–38

    Article  Google Scholar 

  • Robakis D, Fahn S (2015) Defining the role of the monoamine oxidase-B inhibitors for Parkinson’s disease. CNS Drugs. 29(6):433–441

    Article  CAS  PubMed  Google Scholar 

  • Rui Q, Ni H, Li D, Gao R, Chen G (2018) The role of LRRK2 in neurodegeneration of Parkinson disease. Curr Neuropharmacol. 16(9):1348–1357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rukmangathen R, Yallamalli IM, Yalavarthi PR (2019) Biopharmaceutical potential of selegiline loaded chitosan nanoparticles in the management of Parkinson’s disease. Curr Drug Discov Technol. 16(4):417–425

    Article  CAS  PubMed  Google Scholar 

  • Salat D, Tolosa E (2013) Levodopa in the treatment of Parkinson’s disease: current status and new developments. J Parkinsons Dis. 3(3):255–269

    Article  CAS  PubMed  Google Scholar 

  • Sangwan S, Sahay S, Murray KA, Morgan S, Guenther EL, Jiang L et al (2020) Inhibition of synucleinopathic seeding by rationally designed inhibitors. Eisen MB, editor. Elife. 9:e46775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sapru MK, Yates JW, Hogan S, Jiang L, Halter J, Bohn MC (2006) Silencing of human alpha-synuclein in vitro and in rat brain using lentiviral-mediated RNAi. Exp Neurol. 198(2):382–390

    Article  CAS  PubMed  Google Scholar 

  • Saraiva C, Paiva J, Santos T, Ferreira L, Bernardino L (2016) MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson’s disease. J Control Release. 235:291–305

    Article  CAS  PubMed  Google Scholar 

  • Sardi SP, Clarke J, Kinnecom C, Tamsett TJ, Li L, Stanek LM et al (2011) CNS expression of glucocerebrosidase corrects alpha-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy. Proc Natl Acad Sci U S A. 108(29):12101–12106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sardi SP, Cedarbaum JM, Brundin P (2018) Targeted therapies for Parkinson’s disease: from genetics to the clinic. Mov Disord. 33(5):684–696

    Article  PubMed  PubMed Central  Google Scholar 

  • Savola J-M, Hill M, Engstrom M, Merivuori H, Wurster S, McGuire SG et al (2003) Fipamezole (JP-1730) is a potent α2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson’s disease. Mov Disord. 18(8):872–883

    Article  PubMed  Google Scholar 

  • Schapira AHV, Bezard E, Brotchie J, Calon F, Collingridge GL, Ferger B et al (2006) Novel pharmacological targets for the treatment of Parkinson’s disease. Nat Rev Drug Discov. 5(10):845–854

    Article  CAS  PubMed  Google Scholar 

  • Schenk DB, Koller M, Ness DK, Griffith SG, Grundman M, Zago W et al (2017) First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers. Mov Disord. 32(2):211–218

    Article  CAS  PubMed  Google Scholar 

  • Schofield DJ, Irving L, Calo L, Bogstedt A, Rees G, Nuccitelli A et al (2019) Preclinical development of a high affinity α-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular α-synuclein and attenuate α-synuclein spreading in vivo. Neurobiol Dis. 132:104582

    Article  CAS  PubMed  Google Scholar 

  • Schwarzschild MA, Agnati L, Fuxe K, Chen J-F, Morelli M (2006) Targeting adenosine A2A receptors in Parkinson’s disease. Trends Neurosci. 29(11):647–654

    Article  CAS  PubMed  Google Scholar 

  • Scott JD, DeMong DE, Greshock TJ, Basu K, Dai X, Harris J et al (2017) Discovery of a 3-(4-pyrimidinyl) indazole (MLi-2), an orally available and selective leucine-rich repeat kinase 2 (LRRK2) inhibitor that reduces brain kinase activity. J Med Chem. 60(7):2983–2992

    Article  CAS  PubMed  Google Scholar 

  • Seneff S, Nigh G, Kyriakopoulos AM, McCullough PA (2022) Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs. Food Chem Toxicol 164:113008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S et al (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 59(10):1541–1550

    Article  PubMed  Google Scholar 

  • Siddiqui IJ, Pervaiz N, Abbasi AA (2016) The Parkinson disease gene SNCA: Evolutionary and structural insights with pathological implication. Sci Rep. 6:24475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sieradzan KA, Fox SH, Hill M, Dick JPR, Crossman AR, Brotchie JM (2001) Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: A pilot study. Neurology. 57(11):2108–2111

    Article  CAS  PubMed  Google Scholar 

  • Sim CH, Gabriel K, Mills RD, Culvenor JG, Cheng H-C (2012) Analysis of the regulatory and catalytic domains of PTEN-induced kinase-1 (PINK1). Hum Mutat. 33(10):1408–1422

    Article  CAS  PubMed  Google Scholar 

  • Simon DK, Tanner CM, Brundin P (2020) Parkinson disease epidemiology, pathology, genetics, and pathophysiology. Clin Geriatr Med. 36(1):1–12

    Article  PubMed  Google Scholar 

  • Singh G, Sikder A, Phatale V, Srivastava S, Singh SB, Khatri DK (2023) Therapeutic potential of GDNF in neuroinflammation: targeted delivery approaches for precision treatment in neurological diseases. J Drug Deliv Sci Technol 24:104876. https://doi.org/10.1016/j.jddst.2023.104876

    Article  CAS  Google Scholar 

  • Sood A, Preeti K, Fernandes V, Khatri DK, Singh SB (2021) Glia: a major player in glutamate–GABA dysregulation-mediated neurodegeneration. Abstr J Neurosci Res 99(12):3148–3189. https://doi.org/10.1002/jnr.24977

    Article  CAS  Google Scholar 

  • Soukup S-F, Vanhauwaert R, Verstreken P (2018) Parkinson’s disease: convergence on synaptic homeostasis. EMBO J. 37(18):e98960

    Article  PubMed  PubMed Central  Google Scholar 

  • Spiers GF, Kunonga TP, Beyer F, Craig D, Hanratty B, Jagger C (2021) Trends in health expectancies: a systematic review of international evidence. BMJ Open. 11(5):e045567

    Article  PubMed  PubMed Central  Google Scholar 

  • Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ, Jakes R, Goedert M (1997) α-Synuclein in Lewy bodies. Nature. 388(6645):839–840. https://doi.org/10.1038/42166

    Article  CAS  PubMed  Google Scholar 

  • Staal R, Kubek K, Sung A, Lin Q, DenBleyker M, Monaghan M et al (2009) P2.080 DimebonTM is neuroprotective in a model of Parkinson’s disease. Park Relat Disord Park Relat Disord 15

    Google Scholar 

  • Sun L, Xu S, Zhou M, Wang C, Wu Y, Chan P (2010) Effects of cysteamine on MPTP-induced dopaminergic neurodegeneration in mice. Brain Res. 1335:74–82

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131(5):861–872

    Article  CAS  PubMed  Google Scholar 

  • Tanaka MT, Miki Y, Bettencourt C, Ozaki T, Tanji K, Mori F et al (2022) Involvement of autophagic protein DEF8 in Lewy bodies. Biochem Biophys Res Commun. 623:170–175. https://www.sciencedirect.com/science/article/pii/S0006291X22010464

    Article  CAS  PubMed  Google Scholar 

  • Tansey MG, Goldberg MS (2010) Neuroinflammation in Parkinson’s disease: Its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis. 37(3):510–518

    Article  CAS  PubMed  Google Scholar 

  • Tatton W, Chalmers-Redman R, Tatton N (2003) Neuroprotection by deprenyl and other propargylamines: glyceraldehyde-3-phosphate dehydrogenase rather than monoamine oxidase B. J Neural Transm. 110(5):509–515

    Article  CAS  PubMed  Google Scholar 

  • Temel Y (2010) Limbic effects of high-frequency stimulation of the subthalamic nucleus. Vitam Horm. 82:47–63

    Article  PubMed  Google Scholar 

  • Titze-De-almeida SS, Soto-Sánchez C, Fernandez E, Koprich JB, Brotchie JM, Titze-de-almeida R (2020) The promise and challenges of developing miRNA-based therapeutics for Parkinson’s disease. Cells. 9(4):841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tonda-Turo C, Origlia N, Mattu C, Accorroni A, Chiono V (2018) Current limitations in the treatment of Parkinson’s and Alzheimer’s diseases: state-of-the-art and future perspective of polymeric carriers. Curr Med Chem. 25(41):5755–5771

    Article  CAS  PubMed  Google Scholar 

  • Tran TA, McCoy MK, Sporn MB, Tansey MG (2008) The synthetic triterpenoid CDDO-methyl ester modulates microglial activities, inhibits TNF production, and provides dopaminergic neuroprotection. J Neuroinflammation. 5(1):14

    Article  PubMed  PubMed Central  Google Scholar 

  • Tremblay M-E, Saint-Pierre M, Bourhis E, Lévesque D, Rouillard C, Cicchetti F (2006) Neuroprotective effects of cystamine in aged parkinsonian mice. Neurobiol Aging. 27(6):862–870

    Article  CAS  PubMed  Google Scholar 

  • Trempe J-F, Sauvé V, Grenier K, Seirafi M, Tang MY, Ménade M et al (2013) Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science (80- ) 340(6139):1451–1455

    Article  CAS  Google Scholar 

  • Tsai S-J (2007) Glatiramer acetate could be a potential therapeutic agent for Parkinson’s disease through its neuroprotective and anti-inflammatory effects. Med Hypotheses. 69(6):1219–1221

    Article  CAS  PubMed  Google Scholar 

  • Tsou Y-H, Zhang X-Q, Zhu H, Syed S, Xu X (2017) Drug delivery to the brain across the blood–brain barrier using nanomaterials. Small. 13(43):1701921. https://doi.org/10.1002/smll.201701921

    Article  CAS  Google Scholar 

  • Umarao P, Bose S, Bhattacharyya S, Kumar A, Jain S (2016) Neuroprotective potential of superparamagnetic iron oxide nanoparticles along with exposure to electromagnetic field in 6-OHDA rat model of Parkinson’s disease. J Nanosci Nanotechnol. 16(1):261–269

    Article  CAS  PubMed  Google Scholar 

  • van der Groen O, Mattingley JB, Wenderoth N (2019) Altering brain dynamics with transcranial random noise stimulation. Sci Rep. 9(1):4029

    Article  PubMed  PubMed Central  Google Scholar 

  • Vegas-Suárez S, Pisanò CA, Requejo C, Bengoetxea H, Lafuente JV, Morari M et al (2020) 6-Hydroxydopamine lesion and levodopa treatment modify the effect of buspirone in the substantia nigra pars reticulata. Br J Pharmacol. 177(17):3957–3974

    Article  PubMed  PubMed Central  Google Scholar 

  • Vermeiren Y, Deyn D (2017) Targeting the norepinephrinergic system in Parkinson’s disease and related disorders: The locus coeruleus story. Neurochem Int. 102:22–32

    Article  CAS  PubMed  Google Scholar 

  • Vlachos F, Tung Y-S, Konofagou E (2011) Permeability dependence study of the focused ultrasound-induced blood-brain barrier opening at distinct pressures and microbubble diameters using DCE-MRI. Magn Reson Med. 66:821–830

    Article  PubMed  PubMed Central  Google Scholar 

  • Wagner J, Ryazanov S, Leonov A, Levin J, Shi S, Schmidt F et al (2013) Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson’s disease. Acta Neuropathol. 125(6):795–813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wakabayashi K, Mori F, Takahashi H (2006) Progression patterns of neuronal loss and Lewy body pathology in the substantia nigra in Parkinson’s disease. Park Relat Disord 12:S92–S98

    Article  Google Scholar 

  • Wang N, Jin X, Guo D, Tong G, Zhu X (2017) Iron chelation nanoparticles with delayed saturation as an effective therapy for Parkinson disease. Biomacromolecules. 18(2):461–474. https://doi.org/10.1021/acs.biomac.6b01547

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Gao G, Duan C, Yang H (2019) Progress of immunotherapy of anti-α-synuclein in Parkinson’s disease. Biomed Pharmacother. 115:108843

    Article  CAS  PubMed  Google Scholar 

  • Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJJ et al (2009) Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 301(1):63–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weihofen A, Liu Y, Arndt JW, Huy C, Quan C, Smith BA et al (2019) Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson’s disease models. Neurobiol Dis. 124:276–288

    Article  CAS  PubMed  Google Scholar 

  • Weinreb O, Mandel S, Youdim MBH, Amit T (2013) Targeting dysregulation of brain iron homeostasis in Parkinson’s disease by iron chelators. Free Radic Biol Med. 62:52–64

    Article  CAS  PubMed  Google Scholar 

  • Wen Z, Yan Z, Hu K, Pang Z, Cheng X, Guo L et al (2011) Odorranalectin-conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson’s disease following intranasal administration. J Control Release 151(2):131–138

    Article  CAS  PubMed  Google Scholar 

  • Wichmann T, DeLong MR, Guridi J, Obeso JA (2011) Milestones in research on the pathophysiology of Parkinson’s disease. Mov Disord. 26(6):1032–1041

    Article  PubMed  PubMed Central  Google Scholar 

  • Wilhelmus MMM, Verhaar R, Andringa G, Bol JGJM, Cras P, Shan L et al (2011) Presence of Tissue transglutaminase in granular endoplasmic reticulum is characteristic of melanized neurons in Parkinson’s disease brain. Brain Pathol. 21(2):130–139

    Article  CAS  PubMed  Google Scholar 

  • Witte ME, Geurts JJG, de Vries HE, van der Valk P, van Horssen J (2010) Mitochondrial dysfunction: a potential link between neuroinflammation and neurodegeneration? Mitochondrion. 10(5):411–418

    Article  CAS  PubMed  Google Scholar 

  • Wood LD (2010) Clinical review and treatment of select adverse effects of dopamine receptor agonists in Parkinson’s disease. Drugs Aging. 27(4):295–310

    Article  CAS  PubMed  Google Scholar 

  • Wood H (2020) Gene therapy boosts response to levodopa in patients with Parkinson disease. Nat Rev Neurol. 16(5):242

    CAS  PubMed  Google Scholar 

  • Wu RM, Chen RC, Chiueh CC (2000) Effect of MAO-B inhibitors on MPP+ toxicity in Vivo. Ann N Y Acad Sci. 899:255–261

    Article  CAS  PubMed  Google Scholar 

  • Xia Q, Liao L, Cheng D, Duong DM, Gearing M, Lah JJ et al (2008) Proteomic identification of novel proteins associated with Lewy bodies. Front Biosci. 13:3850–3856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan H, Zhang ZW, Liang LW, Shen Q, Wang XD, Ren SM et al (2010) Treatment strategies for Parkinson’s disease. Neurosci Bull. 26(1):66–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yurek D, Hasselrot U, Sesenoglu-Laird O, Padegimas L, Cooper M (2017) Intracerebral injections of DNA nanoparticles encoding for a therapeutic gene provide partial neuroprotection in an animal model of neurodegeneration. Nanomedicine. 13(7):2209–2217

    Article  CAS  PubMed  Google Scholar 

  • Zanin M, Santos BFR, Antony PMA, Berenguer-Escuder C, Larsen SB, Hanss Z et al (2020) Mitochondria interaction networks show altered topological patterns in Parkinson’s disease. NPJ Syst Biol Appl. 6(1):38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeng R, Luo DX, Li HP, Zhang QS, Lei SS, Chen JH (2019) MicroRNA-135b alleviates MPP+-mediated Parkinson’s disease in in vitro model through suppressing FoxO1-induced NLRP3 inflammasome and pyroptosis. J Clin Neurosci. 65(xxxx):125–133

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Sun P, Lin K, Chan FHL, Gao Q, Lau WF et al (2019) Extracellular nanomatrix-induced self-organization of neural stem cells into miniature substantia nigra-like structures with therapeutic effects on Parkinsonian rats. Adv Sci. 6(24):1901822. https://doi.org/10.1002/advs.201901822

    Article  CAS  Google Scholar 

  • Zhang P, Park H-J, Zhang J, Junn E, Andrews RJ, Velagapudi SP et al (2020) Translation of the intrinsically disordered protein α-synuclein is inhibited by a small molecule targeting its structured mRNA. Proc Natl Acad Sci. 117(3):1457–1467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao S, Cheng R, Zheng J, Li Q, Wang J, Fan W et al (2015) A randomized, double-blind, controlled trial of add-on therapy in moderate-to-severe Parkinson’s disease. Parkinsonism Relat Disord. 21(10):1214–1218

    Article  PubMed  Google Scholar 

  • Zhao HT, John N, Delic V, Ikeda-Lee K, Kim A, Weihofen A et al (2017) LRRK2 antisense oligonucleotides ameliorate α-synuclein inclusion formation in a Parkinson’s disease mouse model. Mol Ther Nucleic Acids. 8:508–519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Y, Yang B, Zhou C, Gao C, Hu Y, Yin WF et al (2022) Cortical atrophy is associated with cognitive impairment in Parkinson’s disease: a combined analysis of cortical thickness and functional connectivity. Brain Imaging Behav. 16:2586–2600

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular and Cellular Neuroscience Lab, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)- Hyderabad, Balanagar, Hyderabad, Telangana, India

    Khan Sabiya Samim, Padmashri Naren, Poojitha Pinjala, Sainikil Uppala, Shashi Bala Singh & Dharmendra Kumar Khatri

Authors
  1. Khan Sabiya Samim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Padmashri Naren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Poojitha Pinjala
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sainikil Uppala
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shashi Bala Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dharmendra Kumar Khatri
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, India

    Awanish Mishra

  2. School of Nano Sciences, Central University of Gujarat, Gandhinagar, Gujarat, India

    Hitesh Kulhari

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Samim, K.S., Naren, P., Pinjala, P., Uppala, S., Singh, S.B., Khatri, D.K. (2023). Pathophysiology and Management Approaches for Parkinson’s Disease. In: Mishra, A., Kulhari, H. (eds) Drug Delivery Strategies in Neurological Disorders: Challenges and Opportunities. Springer, Singapore. https://doi.org/10.1007/978-981-99-6807-7_5

Download citation

  • DOI: https://doi.org/10.1007/978-981-99-6807-7_5

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-99-6806-0

  • Online ISBN: 978-981-99-6807-7

  • eBook Packages: MedicineBiomedical and Life Sciences (R0)

Publish with us

Policies and ethics

Search

Navigation