MicroRNA as Potential Biomarkers and Their Pathogenesis in Multiple System Atrophy

Multiple system atrophy (MSA) is a rare, rapidly progressive neurodegenerative disorder characterized by autonomic dysfunction, Parkinsonism, and cerebellar ataxia. While the pathological hallmark of MSA is the accumulation of α-synuclein in oligodendrocytes and formation of glial cytoplasmic inclusions (GCIs), the precise etiopathogenesis, accurate biomarkers, and promising therapeutic targets remain elusive. This review synthesizes current evidence regarding the role of microRNAs (miRNAs) in MSA, focusing on how small non-coding RNAs mediate gene–environment interactions contributing to disease pathogenesis. We explore dysregulated miRNA profiles in MSA, their impact on α-synuclein aggregation, neuroinflammation, demyelinating process, and oligodendrocyte dysfunction, and their potential as biomarkers and therapeutic targets. Understanding the complex interplay between miRNAs, genetic susceptibility, and environmental factors may provide critical insights into MSA pathophysiology and open new avenues for therapeutic intervention.