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

• Published in: International journal of molecular sciences Vol. 23; no. 23; p. 15076
• Main Authors: Kinoshita, Chisato, Kubota, Noriko, Aoyama, Koji
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2022; MDPI
• Subjects: alpha-Synuclein - metabolism; Alzheimer's disease; Antioxidants; Ataxia; Atrophy; Autonomic nervous system; Basal ganglia; Behavior disorders; Brain; Central nervous system; Central nervous system diseases; Cerebellum; Cerebellum - metabolism; Dementia; Depletion; Eye movements; Failure; Gene expression; Glutathione; Humans; microRNA; MicroRNAs; MicroRNAs - genetics; miRNA; multiple system atrophy; Multiple System Atrophy - genetics; Multiple System Atrophy - pathology; Mutation; Nervous system; neurodegenerative disease; Neuromodulation; Neurons; Oxidative stress; Parkinson's disease; Parkinsonian Disorders; Pathogenesis; Pathology; Physiology; Post-transcription; Review; α-synuclein; microRNA; neurodegenerative disease; multiple system atrophy; glutathione; oxidative stress; α-synuclein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232315076

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.