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

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.

Bilirubin and Redox Stress in Age-Related Brain Diseases

“…Ataxia (A-) is a group of symptoms of poor muscle control that usually results from cerebellar or brainstem damage, which can cause problems with walking, balance, coordination, speech, and eye movements [ 199 , 200 ]. Although the causes, onset, and progression of ataxia remain to be fully understood, oxidative stress via the excess generation of ROS and/or disruption of the antioxidant system results in cellular damage ( Figure 4 ) [ 201 ]. It has to be mentioned that HMOX1 hyper-activation and Fe 2+ accumulation have been reported to contribute to specific forms of ataxia, namely Friedreich and posterior column sensory ataxia [ 32 , 37 ].…”