Selective neuronal vulnerability in Parkinson's disease

Patricia Gonzalez-Rodriguez, Enrico Zampese, D. James Surmeier*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease, disabling millions worldwide. Despite the imperative PD poses, at present, there is no cure or means of slowing progression. This gap is attributable to our incomplete understanding of the factors driving pathogenesis. Research over the past several decades suggests that both cell-autonomous and non-cell autonomous processes contribute to the neuronal dysfunction underlying PD symptoms. The thesis of this review is that an intersection of these processes governs the pattern of pathology in PD. Studies of substantia nigra pars compacta (SNc) dopaminergic neurons, whose loss is responsible for the core motor symptoms of PD, suggest that they have a combination of traits—a long, highly branched axon, autonomous activity, and elevated mitochondrial oxidant stress—that predispose them to non-cell autonomous drivers of pathogenesis, like misfolded forms of alpha-synuclein (α-SYN) and inflammation. The literature surrounding these issues will be briefly summarized, and the translational implications of an intersectional hypothesis of PD pathogenesis discussed.

Original languageEnglish (US)
Title of host publicationProgress in Brain Research
EditorsAnders Björklund, M. Angela Cenci
PublisherElsevier B.V.
Pages61-89
Number of pages29
ISBN (Print)9780444642608
DOIs
StatePublished - 2020

Publication series

NameProgress in Brain Research
Volume252
ISSN (Print)0079-6123
ISSN (Electronic)1875-7855

Keywords

  • Aging
  • Axon
  • Calcium
  • Lewy pathology
  • Mitochondrial dysfunction
  • Neurodegeneration
  • Oxidant stress
  • Parkinson's disease
  • Propagation
  • Synapse
  • α-synuclein

ASJC Scopus subject areas

  • Neuroscience(all)

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