Neurodegeneration and neuroprotection in Parkinson disease.
Many of the motoric features that define Parkinson disease (PD) result primarily from the loss of the neuromelanin (NM)-containing dopamine (DA) neurons of the substantia nigra (SN), and to a lesser extent, other mostly catecholaminergic neurons, and are associated with cytoplasmic "Lewy body" inclusions in some of the surviving neurons. While there are uncommon instances of familial PD, and rare instances of known genetic causes, the etiology of the vast majority of PD cases remains unknown (i.e., idiopathic). Here we outline genetic and environmental findings related to PD epidemiology, suggestions that aberrant protein degradation may play a role in disease pathogenesis, and pathogenetic mechanisms including oxidative stress due to DA oxidation that could underlie the selectivity of neurodegeneration. We then outline potential approaches to neuroprotection for PD that are derived from current notions on disease pathogenesis.
Fahn
Stanley
S
Department of Neurology, Columbia University, New York, New York 10032, USA. fahn@neuro.columbia.edu
Sulzer
David
D
D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*
D018696:Neuroprotective Agents
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