Neurodegeneration: Impact of S-nitrosylated Parkin, DJ-1 and PINK1 on the pathogenesis of Parkinson's disease

Esha Sircar, Sristi Raj Rai, Mark A. Wilson, Michael G. Schlossmacher, Rajib Sengupta

Research output: Contribution to journalReview articlepeer-review

Abstract

Parkinson's disease (PD) is one of the fastest-growing neurodegenerative disorders of increasing global prevalence. It represents the second most common movement disorder after tremor and the second most common neurodegenerative disorder after Alzheimer's disease. The incidence rate of idiopathic PD increases steadily with age, however, some variants of autosomal recessive inheritance are present with an early age-at-onset (ARPD). Approximately 50 percent of ARPD cases have been linked to bi-allelic mutations in genes encoding Parkin, DJ-1, and PINK1. Each protein has been implicated in maintaining proper mitochondrial function, which is particularly important for neuronal health. Aberrant post-translational modifications of these proteins may disrupt their cellular functions and thus contributing to the development of idiopathic PD. Some post-translational modifictions can be attributed to the dysregulation of potentially harmful reactive oxygen and nitrogen species inside the cell, which promote oxidative and nitrosative stress, respectively. Unlike oxidative modifications, the covalent modification by Nitric Oxide under nitrosative stress, leading to S-nitrosylation of Parkin, DJ-1; and PINK1, is less studied. Here, we review the available literature on S-nitrosylation of these three proteins, their implications in the pathogenesis of PD, and provide an overview of currently known, denitrosylating systems in eukaryotic cells.

Original languageEnglish (US)
Article number108869
JournalArchives of Biochemistry and Biophysics
Volume704
DOIs
StatePublished - Jun 15 2021

Keywords

  • Glutaredoxin
  • PINK1
  • Parkin, DJ-1
  • Parkinson's disease
  • S-nitrosylation
  • Thioredoxin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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