MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
Prog Lipid Res. 2010 Oct;49(4):420-8. doi: 10.1016/j.plipres.2010.05.004. Epub 2010 May 23.
Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease, among the aging human population. The main symptoms of Parkinson's disease such as tremor and movement disabilities are the result of degeneration of dopaminergic neurons in substantia nigra pars compacta. The widely-accepted subcellular factor which underlies Parkinson's disease neuropathology is the presence of Lewy bodies with characteristic inclusions of aggregated alpha-synuclein. This small soluble protein has been implicated in a range of interactions with phospholipid membranes and free fatty acids. The precise biological function of this protein is, however, still under investigation. Here we review the evidence linking alpha-synuclein, lipid metabolism, fatty acid oxidation, mitochondrial damage and Parkinson's disease. We propose that association of alpha-synuclein with oxidized lipid metabolites can lead to mitochondrial dysfunction in turn leading to dopaminergic neuron death and thus to Parkinson's disease.
帕金森病是仅次于阿尔茨海默病的第二大常见神经退行性疾病，在老龄化人口中较为常见。帕金森病的主要症状，如震颤和运动障碍，是黑质致密部多巴胺能神经元退化的结果。被广泛接受的帕金森病神经病理学的亚细胞因素是路易体的存在，其具有聚集的α-突触核蛋白的特征内含物。这种小的可溶性蛋白已涉及一系列与磷脂膜和游离脂肪酸的相互作用。然而，该蛋白的确切生物学功能仍在研究中。在这里，我们综述了将α-突触核蛋白与脂质代谢、脂肪酸氧化、线粒体损伤和帕金森病联系起来的证据。我们提出，α-突触核蛋白与氧化脂质代谢物的结合可能导致线粒体功能障碍，进而导致多巴胺能神经元死亡，从而导致帕金森病。
