Therapeutic Applications of Exosomal microRNAs in Alzheimer’s, Parkinson’s, and Multiple Sclerosis: A Systematic Comparative Analysis (۲۰۱۴-۲۰۲۴)

Introduction: Neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) lack effective treatments. Exosomal microRNAs (miRNAs), small vesicle-derived regulators of gene expression, have emerged as therapeutic agents for disease treatment due to their ability to cross the blood-brain barrier . To systematically review therapeutic applications of exosomal miRNAs in preclinical models of AD, PD, and MS, identifying key miRNAs, mechanisms of action, and therapeutic outcomes.Data Sources: Literature search in PubMed, Web of Science, and Scopus (January ۲۰۱۴-March ۲۰۲۴) using combinations of exosome, microRNA, and neurodegenerative disease terms.Study Selection: Studies investigating therapeutic applications of exosomal miRNAs in AD, PD, or MS using disease models, examining specific miRNAs and their therapeutic effects, published in English. Reviewers screened studies using predefined criteria.Data Extraction: Data extracted using standardized forms encompassing study characteristics, exosome sources, microRNA information, and outcomes. Quality assessed using modified SYRCLE and JBI tools.Results: Forty studies were included: AD (n = ۲۰), PD (n = ۱۱), and MS (n = ۹). Mesenchymal stem cell-derived exosomes were predominant (۵۵%). In AD, miR-۲۹ and miR-۱۲۴ targeted amyloidogenesis via BACE۱ and NLRP۳ pathways, with cognitive improvement in ۵۵% of studies and ۴۰-۵۰% Aβ reduction. In PD, miR-۷ and miR-۱۰۰a-۵p modulated autophagy and oxidative stress, providing neuroprotection in ۷۲% of studies. In MS, miR-۲۱۹ and miR-۲۳a promoted remyelination in ۶۷% of studies with enhanced oligodendrocyte differentiation and reduced inflammatory markers by ۳۰-۶۰%.Conclusion: Exosomal miRNAs demonstrate significant therapeutic potential for neurodegenerative diseases. Their ability to target pathological pathways positions them as promising candidates for clinical translation.

کلیدواژه ها:

Extracellular vesicles ، Alzheimer Disease ، Parkinson disease ، Multiple Sclerosis ، Systematic review ، Gene Therapy