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Understanding the multifaceted role of miRNAs in Alzheimer’s disease pathology

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Abstract

Small non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation. Since miRNAs can regulate the expression of several genes, they have multiple roles to play in biological processes and human diseases. The majority of miRNAs are known to be expressed in the brain and are involved in synaptic functions, thus marking their presence and role in major neurodegenerative disorders, including Alzheimer’s disease (AD). In AD, amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) are known to be the major hallmarks. The clearance of Aβ and tau is known to be associated with miRNA dysregulation. In addition, the β-site APP cleaving enzyme (BACE 1), which cleaves APP to form Aβ, is also found to be regulated by miRNAs, thus directly affecting Aβ accumulation. Growing evidences suggest that neuroinflammation can be an initial event in AD pathology, and miRNAs have been linked with the regulation of neuroinflammation. Inflammatory disorders have also been associated with AD pathology, and exosomes associated with miRNAs are known to regulate brain inflammation, suggesting for the role of systemic miRNAs in AD pathology. Several miRNAs have been related in AD, years before the clinical symptoms appear, most of which are associated with regulating the cell cycle, immune system, stress responses, cellular senescence, nerve growth factor (NGF) signaling, and synaptic regulation. Phytochemicals, especially polyphenols, alter the expression of various miRNAs by binding to miRNAs or binding to the transcriptional activators of miRNAs, thus control/alter various metabolic pathways. Awing to the sundry biological processes being regulated by miRNAs in the brain and regulation of expression of miRNAs via phytochemicals, miRNAs and the regulatory bioactive phytochemicals can serve as therapeutic agents in the treatment and management of AD.

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Acknowledgements

H.V., S.K., P.G. A.Y. and R.R. acknowledges financial support in the form of a senior/junior research fellowship (SRF/JRF) from the University Grants Commission (UGC), New Delhi and Dept. of Biotechnology (DBT) and Council for Scientific and Industrial Research (CSIR), Govt. of India, New Delhi, India, respectively. Because of the limited focus of the article, many relevant and appropriate references could not be included, for which the authors apologize.

Funding

A.K.M and M.D. thankfully acknowledges financial support in the form of Core Research Grant (CRG/2021/002524) from SERB, DST, Govt. of India, New Delhi, India.

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Author notes

  1. Sharanjot Kaur and Harkomal Verma contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology, School of Basic Sciences, Central University of Punjab, Ghudda, Bathinda, Punjab, India

    Sharanjot Kaur, Sukhchain Kaur & Monisha Dhiman

  2. Department of Zoology, School of Basic Sciences, Central University of Punjab, VPO – Ghudda, Bathinda, 151 401, Punjab, India

    Harkomal Verma, Prabhakar Gangwar, Anuradha Yadav, Bharti Yadav, Rashmi Rao & Anil Kumar Mantha

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Contributions

AKM and MD conceived the idea and outline of the manuscript. SK and HV (both of them contributed equally) performed literature review, wrote the manuscript and made the figures and tables along with SK, PG, AY, BY, and RR. All authors have read the manuscript and agreed to the final draft of the manuscript.

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Correspondence to Anil Kumar Mantha.

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Kaur, S., Verma, H., Kaur, S. et al. Understanding the multifaceted role of miRNAs in Alzheimer’s disease pathology. Metab Brain Dis 39, 217–237 (2024). https://doi.org/10.1007/s11011-023-01265-9

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