Abstract
Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the death of dopaminergic neurons. Its pathogenesis comprises defects in the physiological pathway of mitophagy and mutations in the genes involved in this process’s regulatory mechanism. PD manifests itself with multiple motor and non-motor symptoms, and currently, there are multiple pharmacological treatments, and unconventional non-drug treatments available. The mainstay of Parkinson’s disease treatment has centered around directly manipulating neural mechanisms to retain high dopamine levels, either by exogenous administration, increasing intrinsic production, or inhibiting the breakdown of dopamine. In this review, we highlight a new potential biochemical modality of treatment, treating PD through glycolysis. We highlight how terazosin (TZ), via PGK1, increases ATP levels and how enhanced glycolysis serves a neuroprotective role in PD, and compensates for damage caused by mitophagy. We also discuss the role of quercetin, a bioactive flavonoid, in preventing the development of PD, and reversing mitochondrial dysfunction but only so in diabetic patients. Thus, further research should be conducted on glycolysis as a protective target in PD that can serve to not just prevent, but also alleviate the non-dopaminergic signs and symptoms of PD.
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Abbreviations
- PD:
-
Parkinson’s disease
- BPH:
-
Benign prostate hyperplasia
- MPTP:
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- 6-OHDA:
-
6-Hydroxydopamine
- PINK1:
-
PTEN-induced kinase 1
- LRRK2:
-
Leucine-rich repeat kinase 2
- WT:
-
Wilms’ tumor protein
- PGK-1:
-
Phosphoglycerate kinase 1
- PARKIN:
-
Parkinson’s juvenile disease protein 2
- PINK1:
-
PTEN-induced kinase 1
- ROS:
-
Reactive oxygen species
- VDAC1:
-
Voltage-dependent anion-selective channel 1
- PARL:
-
Presenilins-associated rhomboid-like protein L-DOPA: Levodopa
- MAO-B:
-
Monoamine oxidase-B
- COMT:
-
Catechol-O-methyltransferase GDNF: Glial cell-derived neurotrophic factor NRTN: Neurturin
- PRF:
-
Proanthocyanidin-rich fraction
- DBS:
-
Deep brain stimulation
- PT:
-
Physiotherapy
- VAS:
-
Visual Analogue Scale
- RCT:
-
Randomized controlled trial
- OT:
-
Occupational therapy
- PGK:
-
Phosphoglycerate kinase
- PK:
-
Pyruvate kinase
- HK:
-
Hexokinase
- PFK:
-
Phosphofructokinase
- PGK-1:
-
Phosphoglycerate kinase 1
- GA3PDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
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We would like to thank Yumna Waseem for helping us with Fig. 1 in this paper.
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Authors Unaiza Naeem, Abdul Rehman Arshad, Areesha Jawed, Farea Eqbal, Laiba Imran, and Zayeema Khan performed the literature search for the review. Additionally. Unaiza Naeem did the conceptualizing of the paper, Farea Eqbal sorted the references in chronological order, and Laiba Imran did the correspondence. All authors were involved in writing the manuscript and the manuscript was reviewed by the senior author, Farhat Ijaz.
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Naeem, U., Arshad, A.R., Jawed, A. et al. Glycolysis: The Next Big Breakthrough in Parkinson’s Disease. Neurotox Res 40, 1707–1717 (2022). https://doi.org/10.1007/s12640-022-00579-3
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DOI: https://doi.org/10.1007/s12640-022-00579-3