Etiopathogenesis of Parkinson disease: A new beginning?

Weidong Le, Shen Chen, Joseph Jankovic

Research output: Contribution to journalReview articlepeer-review

68 Scopus citations


Parkinson disease (PD) probably represents a syndrome of different disorders and origins converging into a relatively uniform neurodegenerative process. Although clinical-pathological studies have suggested that the presymptomatic phase of PD may be relatively short, perhaps less than a decade, the authors postulate that the pathogenic mechanisms may begin much earlier, possibly even in the prenatal period. Thus, some patients with PD may be born with a fewer than normal number of dopaminergic (and nondopaminergic) neurons as a result of genetic or other abnormalities sustained during the prenatal or perinatal period; as a result of normal age-related neuronal attrition, they eventually reach the critical threshold (60% or more) of neuronal loss needed for onset of PD to become clinically manifest. The authors review the emerging evidence that genetic disruption of normal development, coupled with subsequent environmental factors (the so called multiple-hit hypothesis), plays an important role in the etiopathogenesis of PD.

Original languageEnglish (US)
Pages (from-to)28-35
Number of pages8
Issue number1
StatePublished - Feb 1 2009


  • Dopamine neuron development
  • Environmental neurotoxins
  • Gene regulation
  • Transcription factors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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