Vulnerability to Parkinson's Disease: Towards an Unifying Theory of Disease Etiology

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Parkinson's disease (PD) is the most common neurodegenerative disorder affecting approximately 1% of the population over age 65. It is characterized by the selective loss of dopamine-containing neurons in a restricted region of the midbrain called the substantia nigra pars compacta (SNpc). Several genes that cause certain forms of inherited PD (<10% cases) have been identified (including α-synuclein, parkin, DJ-1, and Pink1), and many of them code for proteins implicated in mitochondrial function. However, most cases (>90%) appear to be sporadic and are likely to represent an interplay between genetic and environmental influences. More men than women develop PD; aging and menopause in women (estrogen deficiency) are the recognized risk factors. Polymorphisms in candidate genes involved in dopamine metabolism, mitochondrial function, lipoprotein metabolism, inflammation, and xenobiotic detoxification have been described. In addition, living in rural areas and pesticides exposure, head injury, and infectious diseases during childhood have also been suggested to increase risk; whereas smoking and consumption of coffee, dietary factors, exercising, social interactions, and use of certain nonsteroidal anti-inflammatory drugs reportedly reduce the incidence of PD. Neuropathological studies and animal models highlight neuroinflammation and the astroglial cell compartment as key players in these processes. The overall information points toward glia and its mediators as the final common pathway of gene×environment interactions directing toward neurodegeneration or neuroprotection and neurorepair.

Original languageEnglish
Title of host publicationEncyclopedia of Environmental Health
PublisherElsevier Inc.
Pages690-704
Number of pages15
ISBN (Print)9780444522726
DOIs
Publication statusPublished - Jan 1 2011

Keywords

  • Astroglia
  • Dopaminergic neurons
  • Early embryonic life
  • Environmental toxins
  • Genes
  • Hormones
  • MPTP
  • Neurodegeneration
  • Neurogenesis
  • Neuroinflammation
  • Neuroprotection
  • Neurorepair
  • Parkinson's disease

ASJC Scopus subject areas

  • Environmental Science(all)

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