Journal
NEUROSCIENTIST
Volume 15, Issue 1, Pages 28-35Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1073858408319974
Keywords
transcription factors; gene regulation; dopamine neuron development; environmental neurotoxins
Categories
Funding
- National Institutes of Health [NS043567]
- Michael J. Fox Foundation
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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.
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