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Glutathione Depletion and MicroRNA Dysregulation in Multiple System Atrophy: A Review

Journal

Publisher

MDPI
DOI: 10.3390/ijms232315076

Keywords

multiple system atrophy; neurodegenerative disease; glutathione; microRNA; oxidative stress; alpha-synuclein

Funding

  1. Takeda Science Foundation

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Multiple system atrophy is a rare neurodegenerative disease that is characterized by oxidative stress, glutathione deficiency, and dysregulation of miRNA. These factors are closely related to the pathology of MSA.
Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by parkinsonism, cerebellar impairment, and autonomic failure. Although the causes of MSA onset and progression remain uncertain, its pathogenesis may involve oxidative stress via the generation of excess reactive oxygen species and/or destruction of the antioxidant system. One of the most powerful antioxidants is glutathione, which plays essential roles as an antioxidant enzyme cofactor, cysteine-storage molecule, major redox buffer, and neuromodulator, in addition to being a key antioxidant in the central nervous system. Glutathione levels are known to be reduced in neurodegenerative diseases. In addition, genes regulating redox states have been shown to be post-transcriptionally modified by microRNA (miRNA), one of the most important types of non-coding RNA. miRNAs have been reported to be dysregulated in several diseases, including MSA. In this review, we focused on the relation between glutathione deficiency, miRNA dysregulation and oxidative stress and their close relation with MSA pathology.

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