FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2005
Acetylcholinesterase/paraoxonase interactions increase the risk of insecticide-induced Parkinson's disease.
СтатьяПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Benmoyal-Segal Liat, Vander Tatiana, Shifman Sagiv, Bryk Boris, Ebstein Richard P, Marcus Esther-Lee, Stessman Jochanan, Darvasi Ariel, Herishanu Yuval, Friedman Alon, Soreq Hermona
Аннотация
Exposure to agricultural insecticides, together with yet incompletely understood predisposing genotype/phenotype elements, notably increase the risk of Parkinson's disease. Here, we report findings attributing the increased risk in an insecticide-exposed rural area in Israel to interacting debilitating polymorphisms in the ACHE/PON1 locus and corresponding expression variations. Polymorphisms that debilitate PON1 activity and cause impaired AChE overproduction under anticholinesterase exposure were strongly overrepresented in patients from agriculturally exposed areas, indicating that they confer risk of Parkinson's disease. Supporting this notion, serum AChE and PON1 activities were both selectively and significantly lower in patients than in healthy individuals and in carriers of the risky polymorphisms as compared with other Parkinsonian patients. Our findings suggest that inherited interactive weakness of AChE and PON1 expression increases the insecticide-induced occurrence of Parkinson's disease.