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|Title:||Environmental and genetic interactions: Key to sporadic parkinson's disease?||Authors:||Tsang, F.
Wah Soong, T.
|Issue Date:||2007||Citation:||Tsang, F., Wah Soong, T. (2007). Environmental and genetic interactions: Key to sporadic parkinson's disease?. Oxidative Stress and Neurodegenerative Disorders : 607-619. ScholarBank@NUS Repository. https://doi.org/10.1016/B978-044452809-4/50167-8||Abstract:||Parkinson's disease (PD) is a relentlessly progressive neurodegenerative disorder estimated to be affecting 1% of the population worldwide above the age of 60. PD is largely a sporadic disorder and its specific etiology is incompletely understood. Although familial and sporadic forms of PD are clinically and pathologically distinctive from each other, they tend to share many overlapping features, including nigrostriatal dopaminergic degeneration, which suggests common pathogenic mechanisms between the familial and sporadic forms of PD. A growing body of evidence has indicated mitochondrial dysfunction and oxidative stress (OS) as key players underlying the various mechanisms leading to the development of PD. Mitochondrial dysfunction has long been implicated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated PD. The active metabolite of MPTP, the 1-methyl-4-phenylpyridinium ion (MPP+), is an inhibitor of mitochondrial complex I. Critically, MPTP toxicity, although acute, provides a hint to understanding sporadic PD because complex I impairment in substantial nigra of PD cases has been reported. In addition, there is a close relationship between α-synuclein and OS in the pathogenesis of PD. Recent identification of mutations in DJ-1 and phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) in PD cases lends strong support to the indication of mitochondrial dysfunction and OS as primary factors in the underlying mechanisms leading to PD. This chapter develops some insights into the implications of environmental factors-with emphasis on iron-to molecular mechanisms underlying PD pathogenesis and their potential interaction with genetic factors to the selective susceptibility of dopaminergic neurons in PD. © 2007 Elsevier B.V. All rights reserved.||Source Title:||Oxidative Stress and Neurodegenerative Disorders||URI:||http://scholarbank.nus.edu.sg/handle/10635/109787||ISBN:||9780444528094||DOI:||10.1016/B978-044452809-4/50167-8|
|Appears in Collections:||Staff Publications|
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