Cysteine modifications in the pathogenesis of ALS

Research output: Contribution to journalReview article

Abstract

Several proteins are found misfolded and aggregated in sporadic and genetic forms of amyotrophic lateral sclerosis (ALS). These include superoxide dismutase (SOD1), transactive response DNA-binding protein (TDP-43), fused in sarcoma/translocated in liposarcoma protein (FUS/TLS), p62, vasolin-containing protein (VCP), Ubiquilin-2 and dipeptide repeats produced by unconventional RAN-translation of the GGGGCC expansion in C9ORF72. Up to date, functional studies have not yet revealed a common mechanism for the formation of such diverse protein inclusions. Consolidated studies have demonstrated a fundamental role of cysteine residues in the aggregation process of SOD1 and TDP43, but disturbance of protein thiols homeostatic factors such as protein disulfide isomerases (PDI), glutathione, cysteine oxidation or palmitoylation might contribute to a general aberration of cysteine residues proteostasis in ALS. In this article we review the evidence that cysteine modifications may have a central role in many, if not all, forms of this disease.

Original languageEnglish
Article number5
JournalFrontiers in Molecular Neuroscience
Volume10
DOIs
Publication statusPublished - Jan 23 2017

Keywords

  • Amyotrophic lateral sclerosis
  • Cysteine
  • Neurodegeneration
  • Protein aggregation
  • Superoxide dismutase 1
  • TDP43

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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