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Review
. 2022 Dec 1;23(23):15076.
doi: 10.3390/ijms232315076.

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

Chisato Kinoshita  1 , Noriko Kubota  1   2 , Koji Aoyama  1
Affiliations
Review

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

Chisato Kinoshita et al. Int J Mol Sci. .

Abstract

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.

Keywords: glutathione; microRNA; multiple system atrophy; neurodegenerative disease; oxidative stress; α-synuclein.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Clinical and pathological features of MSA.
Figure 2
Figure 2
Association between the state of α-synuclein and conversion of GSH and GSSG.
Figure 3
Figure 3
Biosynthesis of intracellular glutathione in neurons, microglia and oligodendrocytes. (a) Glutathione (GSH) is comprised of three amino acids: cysteine (Cys), glutamate (Glu) and glycine (Gly), of which Cys is rate-limiting, with its uptake mainly mediated by EAAC1. ASCT1 also contributes to Cys uptake, but its ability might be more limited. Transported Cys is conjugated with Glu catalyzed by glutamate-cysteine ligase (GCL) and then couples with Gly to form GSH. (b) EAAC1 and ASCT1 are members of the SLC1A family, comprised of excitatory amino acid transporter (EAAT) and neutral amino acid transporter (ASCT) subtypes.
Figure 4
Figure 4
Canonical and non-canonical pathways of microRNA biogenesis.
Figure 5
Figure 5
Strategies for early diagnosis and treatment of MSA.
See this image and copyright information in PMC

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