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◆ Cells2025-12-10· Neurodegeneration

Pathological and Molecular Insights into the Early Stage of Multiple System Atrophy

Makoto Timon Tanaka, Yasuo Miki, Tomoya Kon, Fumiaki Mori, Koichi Wakabayashi

原始摘要(英文原文)· Original abstract
Recently, studies have increasingly focused on neuropathological and molecular alterations that occur in the early stages of neurodegenerative diseases to understand the primary pathogenesis. This review provides an updated overview of the early pathological and molecular changes in multiple system atrophy (MSA), a neurodegenerative condition characterised by the degeneration of both the striatonigral and olivopontocerebellar systems. In advanced stages of MSA, abnormal α-synuclein accumulates in the cytoplasm and nuclei of oligodendrocytes and neurones. However, in addition to these established pathological hallmarks, previous analyses of preclinical MSA cases have revealed characteristic accumulations of abnormal α-synuclein within and adjacent to the nuclear membrane. Moreover, analyses of cerebrospinal fluid and plasma from patients with MSA within 3 years of disease onset have identified alterations in various proteins and microRNAs linked to neurodegeneration and neuroinflammation. Consistent with these findings, in vitro and in vivo models of early-stage MSA have demonstrated abnormalities in neurodegeneration, neuroinflammation, and mitochondrial function. Collectively, these observations highlight the primary pathogenesis of early-stage MSA.
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