SOD1 oligomers in amyotrophic lateral sclerosis. (February 2021)

• Record Type: Journal Article
• Authors: Choi, Esther S; Dokholyan, Nikolay V
• Is Part Of: Current opinion in structural biology. Volume 66(2021)
• Page Start: 225
• Page End: 230
• Publication Date: 2021-02
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2020.12.002
• Languages: English
• ISSNs: 0959-440X

Abstract

Graphical abstract: Highlights: SOD1 trimers are the toxic species responsible for cell death rather than large aggregates. Stability of the native SOD1 dimer decreases cellular toxicity whereas increased SOD1 trimer stability increases cellular toxicity. SOD1 trimer formation is not fully understood, but direct interaction of the trimers affects cellular function. Inhibition of SOD1 trimer interactions hold promise as a therapeutic approach. Abstract : Identifying nonnative, trimeric forms of SOD1 trimers as the toxic species, rather than large aggregates revolutionizes our understanding of ALS pathophysiology. Large protein aggregates, what was previously thought as the central cause of neurodegeneration, play protective role and are not responsible for neuronal death. SOD1 trimers are implicated at the molecular, cellular, and organismal level. Understanding the formation of the nonnative trimer and its role in the cell, leading to cell death, holds the key to developing a new standard of therapeutics for ALS and for other neurodegenerative diseases. This review highlights recent advances of knowledge for the role of SOD1 oligomers in ALS.