Ion-catalyzed reactive oxygen species in sporadic models of parkinson’s disease

Velmarini Vasquez, Joy Mitra, Erika N. Guerrero, Pavana M. Hegde, K. S. Rao, Muralidhar L. Hegde

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Parkinson’s disease (PD) is characterized by high concentration of transition metals, mainly prooxidant iron (Fe) and copper (Cu) in the brain, resulting in oxidative stress (OS) and accumulation of oxidative damage to biomolecules, in the degenerating nigral dopaminergic (DAergic) neurons. More recent studies have implicated a marked increase in mitochondrial dysfunction in PD, which further exacerbate reactive oxygen species (ROS) production. Misfolding/aggregation of alpha-synuclein (α-Syn), a hallmark amyloidogenic protein component of Lewy bodies (LBs) in PD DAergic neurons, contributes to oxygen species (OS) and mitochondrial dysfunction. Metal ions and reactive oxygen species (ROS) have been shown to act as “double whammy” in DAergic neurons by not only inducing genome and protein damage but also inhibiting their repair/salvage pathways. While a plethora of evidence has established multiple etiologies and pathological events during PD progression, the cross talk among these various factors and the phenomenon is still obscure, creating a roadblock for effective intervention strategies. In this review, we discuss the current understanding of molecular pathobiology of PD with a primary focus on metal ions/ROS-mediated toxic pathways. Gaps in current knowledge as well as complexities and challenges associated with PD research and potential future directions for improved therapeutic interventions are critically debated.

Original languageEnglish (US)
Title of host publicationMitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease
PublisherSpringer International Publishing
Pages75-113
Number of pages39
ISBN (Electronic)9783319421391
ISBN (Print)9783319421377
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)
  • Agricultural and Biological Sciences(all)

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