Protein Oxidation Triggers the Unfolded Protein Response and Neuronal Injury in Chemically Induced Parkinson Disease

Alison I. Bernstein, Karen L. O’Malley

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


The recent identification of genetic mutations linked to Parkinson’s disease (PD), such as α-synuclein, parkin, and LRRK2, has highlighted the role of aberrant protein handling and degradation in this disorder. Moreover, a growing body of data suggests that environmental toxins that mimic PD also exhibit faulty protein handling, providing a mechanistic link between toxicity and the identified PD mutations. In particular, toxin-mediated cell stress and/or some PD mutations can trigger unfolded protein response, a cell-protective mechanism intended for surviving short-term cellular perturbations. If this process cannot overcome the insult, it is thought that apoptosis is rapidly activated. Although the toxicity of several parkinsonian mimetics is thought to stem from the production of reactive oxygen species, whether oxidative stress and other forms of cell stress are subsequent or parallel events is not well established. Emerging data collected using molecular, biochemical, and cellular techniques suggest that oxidative stress precedes the appearance of unfolded protein response which, in turn, precedes apoptosis. Knowledge of the signaling pathways utilized by parkinsonian mimetics as well as their temporal induction may aid in designing more effective interventions in models of PD and ultimately to treat PD in humans.

Original languageEnglish
Title of host publicationContemporary Clinical Neuroscience
PublisherSpringer Nature
Number of pages14
StatePublished - 2009

Publication series

NameContemporary Clinical Neuroscience
ISSN (Print)2627-535X
ISSN (Electronic)2627-5341


  • 6-OHDA
  • Apoptosis
  • ER stress
  • MPTP
  • Reactive oxygen species
  • UPR


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