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Dysregulated miRNAs in Progression and Pathogenesis of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is a progressive degeneration of neurons due to the accumulation of amyloid-β peptide (Aβ) and hyper-phosphorylation of tau protein in the neuronal milieu leading to increased oxidative stress and apoptosis. Numerous factors contribute towards the progression of AD, including miRNA, which are 22–24 nucleotides long sequence which acts as critical regulators of cellular processes by binding to 3′ UTR of mRNA, regulating its expression post-transcriptionally. This review aims to determine the miRNA with the most significant dysregulation in the brain and cerebrospinal fluid (CSF) of human patients. A systemized inclusion/exclusion criterion has been utilized based on selected keywords followed by screening of those articles to conclude a list of 8 highly dysregulated miRNAs based on the fold change of AD vs control patients, which could be used in clinical testing as these miRNAs play central role in the pathophysiology of AD. Furthermore, a network study of highly dysregulated miRNA estimated the association of these miRNA in the mediation of Aβ generation and aggregation, inhibition of autophagy, reduction of Aβ clearance, microglial and astrocytic activation, neuro-inflammation, tau hyper-phosphorylation, and synaptic loss.

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Acknowledgements

TA is grateful to CSIR for the JRF to carry out this work. RS is also thankful to CSIR for the JRF to carry out this work. VP is thankful to SERB, DST, for the Junior and Senior Research Fellowship.

Funding

Dr. Jyoti Parkash is thankful to the UGC for the UGC startup grant (F.30–312/2016 (BSR)) and Science and Engineering Research Board or SERB (Early Carrier Research Grant, and Core Research Grant (CRG/2020/003257, CRG/2015/000240), Department of Science and Technology, New Delhi, for providing financial assistance.

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Authors and Affiliations

  1. Department of Zoology, School of Biological Sciences, Central University of Punjab, Ghudda 151 401, Bathinda, Punjab, India

    Tania Arora, Vikash Prashar, Randeep Singh, Tushar Singh Barwal & Jyoti Parkash

  2. Department of Biochemistry and Molecular Biology, Guru Nanak Dev University, Amritsar, 143101, Punjab, India

    Harish Changotra

  3. Department of Computational Biology, School of Biological Sciences, Central University of Punjab, Ghudda 151 401, Bathinda, Punjab, India

    Arti Sharma

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  1. Tania Arora
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  2. Vikash Prashar
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  4. Tushar Singh Barwal
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  5. Harish Changotra
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  7. Jyoti Parkash
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Contributions

The data collection and sorting has been done by TA and TSB; final editing has been done by VP, RA, and AS; TSB, HC, and JP helped in proof reading.

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Correspondence to Jyoti Parkash.

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Arora, T., Prashar, V., Singh, R. et al. Dysregulated miRNAs in Progression and Pathogenesis of Alzheimer’s Disease. Mol Neurobiol 59, 6107–6124 (2022). https://doi.org/10.1007/s12035-022-02950-z

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  • DOI: https://doi.org/10.1007/s12035-022-02950-z

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