Department of Biological Chemistry, University of Padova, Italy.
Biofactors. 2011 May-Jun;37(3):228-40. doi: 10.1002/biof.159. Epub 2011 Jun 14.
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNPC) and the presence of intracytoplasmatic inclusions known as Lewy bodies, largely composed of alpha-synuclein (α-syn). PD is a multifactorial disease and its etiology remains largely elusive. Although more than 90% of the cases are sporadic, mutations in several nuclear encoded genes have been linked to the development of autosomal recessive and dominant familial parkinsonian syndromes (Bogaerts et al. (2008) Genes Brain Behav 7, 129-151), enhancing our understanding of biochemical and cellular mechanisms contributing to the disease. Many cellular mechanisms are thought to be involved in the dopaminergic neuronal death in PD, including oxidative stress, intracellular Ca(2+) homeostasis impairment, and mitochondrial dysfunctions. Furthermore, endoplasmic reticulum (ER) stress together with abnormal protein degradation by the ubiquitin proteasome system is considered to contribute to the PD pathogenesis. This review covers all the aspects related to the molecular mechanisms underlying the interplay between mitochondria, ER, and proteasome system in PD-associated neurodegeneration.
帕金森病（PD）是一种进行性神经退行性疾病，其特征是黑质致密部（SNPC）中的多巴胺能神经元丧失和称为路易体的细胞内包涵体的存在，主要由α-突触核蛋白（α-syn）组成。PD 是一种多因素疾病，其病因在很大程度上仍难以捉摸。尽管超过 90%的病例为散发性，但已发现几种核编码基因的突变与常染色体隐性和显性家族性帕金森综合征的发生有关（Bogaerts 等人，2008 年，《基因大脑行为》，第 7 卷，第 129-151 页），这增强了我们对导致疾病的生化和细胞机制的理解。许多细胞机制被认为与 PD 中的多巴胺能神经元死亡有关，包括氧化应激、细胞内 Ca（2+）稳态失调和线粒体功能障碍。此外，内质网（ER）应激以及泛素蛋白酶体系统的异常蛋白降解被认为有助于 PD 的发病机制。本综述涵盖了与 PD 相关神经退行性变中线粒体、ER 和蛋白酶体系统之间相互作用的分子机制相关的所有方面。
