Emamzadeh Fatemeh Nouri
Division of Biomedical and Life Sciences, Faculty of Health and Medicine, University of Lancaster, Lancaster, LA1 4AY, UK.
J Mol Neurosci. 2017 Aug;62(3-4):344-355. doi: 10.1007/s12031-017-0942-9. Epub 2017 Jul 10.
Parkinson's disease (PD) is a progressive brain disorder that interferes with activities of normal life. The main pathological feature of this disease is the loss of more than 80% of dopamine-producing neurons in the substantia nigra (SN). Dopaminergic neuronal cell death occurs when intraneuronal, insoluble, aggregated proteins start to form Lewy bodies (LBs), the most important component of which is a protein called α-synuclein (α-syn). α-Syn structurally contains hexameric repeats of 11 amino acids, which are characteristic of apolipoproteins and thus α-syn can also be considered an apolipoprotein. Moreover, apolipoproteins seem to be involved in the incidence and development of PD. Some apolipoproteins such as ApoD have a neuroprotective role in the brain. In PD, apoD levels increase in glial cells surrounding dopaminergic cells. However, elevated levels of some other apolipoproteins such as ApaA1 and ApoE are reported as a vulnerability factor of PD. At present, when a clinical diagnosis of PD is made, based on symptoms such as shaking, stiff muscles and slow movement, serious damage has already been done to nerve cells of the SN. The diagnosis of PD in its earlier stages, before this irreversible damage, would be of enormous benefit for future treatment strategies designed to slow or halt the progression of PD. This review presents the roles of apolipoproteins and α-syn in PD and how some of them could potentially be used as biomarkers for PD.
帕金森病(PD)是一种进行性脑部疾病,会干扰正常生活活动。这种疾病的主要病理特征是黑质(SN)中80%以上产生多巴胺的神经元丧失。当神经元内不可溶的聚集蛋白开始形成路易小体(LBs)时,多巴胺能神经元细胞就会死亡,路易小体的最重要成分是一种名为α-突触核蛋白(α-syn)的蛋白质。α-突触核蛋白在结构上包含11个氨基酸的六聚体重复序列,这是载脂蛋白的特征,因此α-突触核蛋白也可被视为一种载脂蛋白。此外,载脂蛋白似乎与帕金森病的发生和发展有关。一些载脂蛋白,如载脂蛋白D(ApoD),在大脑中具有神经保护作用。在帕金森病中,多巴胺能细胞周围的胶质细胞中载脂蛋白D水平会升高。然而,据报道,一些其他载脂蛋白,如载脂蛋白A1(ApaA1)和载脂蛋白E(ApoE)水平升高是帕金森病的一个易患因素。目前,当根据震颤、肌肉僵硬和运动迟缓等症状做出帕金森病的临床诊断时,黑质的神经细胞已经受到了严重损害。在这种不可逆转的损害发生之前对帕金森病进行早期诊断,对于未来旨在减缓或阻止帕金森病进展的治疗策略将具有巨大益处。本综述介绍了载脂蛋白和α-突触核蛋白在帕金森病中的作用,以及它们中的一些如何有可能被用作帕金森病的生物标志物。