Oxidative stress factors in Parkinson's disease  

作　　者：Jolanta Dorszewska Marta Kowalska Michał Prendecki Thomas Piekut Joanna Kozłowska Wojciech Kozubski 

机构地区：[1]Laboratory of Neurobiology,Department of Neurology,Poznan University of Medical Sciences,Poznan,Poland [2]Chair and Department of Neurology,Poznan University of Medical Sciences,Poznan,Poland

出　　处：《Neural Regeneration Research》2021年第7期1383-1391,共9页中国神经再生研究（英文版）

基　　金：supported by the grant of NCBi R(European Union), No.POWR.03.01.00-00-T006/18-00。

摘　　要：Parkinson's disease(PD) is the second most common cause of neurodegeneration.Over the last two decades, various hypotheses have been proposed to explain the etiology of PD.Among these is the oxidant-antioxidant theory, which asserts that local and systemic oxidative damage triggered by reactive oxygen species and other free radicals may promote dopaminergic neuron degeneration.Excessive reactive oxygen species formation, one of the underlying causes of pathology in the course of PD has been evidenced by various studies showing that oxidized macromolecules including lipids, proteins, and nucleic acids accumulate in brain tissues of PD patients.DNA oxidation may produce various lesions in the course of PD.Mutations incurred as a result of DNA oxidation may further enhance reactive oxygen species production in the brains of PD patients, exacerbating neuronal loss due to defects in the mitochondrial electron transport chain, antioxidant depletion, and exposure to toxic oxidized dopamine.The protein products of SNCA, PRKN, PINK1, DJ1, and LRRK2 genes are associated with disrupted oxidoreductive homeostasis in PD.SNCA is the first gene linked with familial PD and is currently known to be affected by six mutations correlated with the disorder: A53T, A30P, E46K, G51D, H50Q and A53E.PRKN encodes Parkin, an E3 ubiquitin ligase which mediates the proteasome degradation of redundant and disordered proteins such as glycosylated α-synuclein.Over 100 mutations have been found among the 12 exons of PRKN.PINK1, a mitochondrial kinase highly expressed in the brain, may undergo loss of function mutations which constitute approximately 1–8% of early onset PD cases.More than 50 PD-promoting mutations have been found in PINK1.Mutations in DJ-1, a neuroprotective protein, are a rare cause of early onset PD and constitute only 1% of cases.Around 20 mutations have been found in DJ1 among PD patients thus far.Mutations in the LRRK2 gene are the most common known cause of familial autosomal dominant PD and sporadic PD.Treatment of PD pa

关 键 词：genetic factors molecular parameters oxidative stress Parkinson's disease PHARMACOTHERAPY surgical therapies 

分 类 号：R742.5[医药卫生—神经病学与精神病学]