The environment and Parkinson's disease: is the nigrostriatal system preferentially targeted by neurotoxins?
Recent epidemiological and experimental studies have renewed interest in the hypothesis that the environment has a role in the pathogenesis of Parkinson's disease (PD). Epidemiological studies have identified protective associations (eg, smoking) as well as adverse risk factors (eg, pesticide exposure) for PD. The concordance rate of PD in pairs of dizygotic twins is similar to that in pairs of monozygotic twins, supporting a role of non-genetic risk factors. New models of selective nigrostriatal damage--such as neurotoxicity induced by rotenone or paraquat--have emphasised that environmental agents may contribute to the neurodegenerative process in PD. Toxins interact, in vitro and in vivo, with alpha-synuclein, an endogenous protein that is implicated in pathology of PD. Similarities between clinical and experimental findings, such as the role of pesticide exposure as a potential environmental risk factor, highlight the importance of a multidisciplinary approach to the aetiology of PD.
Di Monte
Donato A
DA
Parkinson's Institute, Sunnyvale, CA 94089, USA. ddimonte@parkinsonsinstitute.org
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D004781:Environmental Exposure / Q000009:adverse effects*; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D007306:Insecticides / Q000633:toxicity; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D009498:Neurotoxins / Q000633:toxicity*; D015513:Oncogene Proteins / Q000235:genetics; D010269:Paraquat / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D012307:Risk Factors; D012402:Rotenone / Q000494:pharmacology / Q000633:toxicity; D051843:Synucleins; D018433:Twin Studies as Topic; D051844:alpha-Synuclein
D006540:Herbicides; D007306:Insecticides; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D015513:Oncogene Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D012402:Rotenone; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D010269:Paraquat