Laboratory of Biochemistry and Functional Proteomics, Department of Science and High Technology, University of Insubria, via Manara,7, I-21052, Busto Arsizio, VA, Italy.
Center of Neuroscience, University of Insubria, Busto Arsizio, Italy.
Mol Neurobiol. 2018 Jan;55(1):370-381. doi: 10.1007/s12035-016-0326-0. Epub 2016 Dec 21.
Neurodegenerative diseases are characterized by the progressive loss of specific neurons in selected regions of the central nervous system. The main clinical manifestation (movement disorders, cognitive impairment, and/or psychiatric disturbances) depends on the neuron population being primarily affected. Parkinson's disease is a common movement disorder, whose etiology remains mostly unknown. Progressive loss of dopaminergic neurons in the substantia nigra causes an impairment of the motor control. Some of the pathogenetic mechanisms causing the progressive deterioration of these neurons are not specific for Parkinson's disease but are shared by other neurodegenerative diseases, like Alzheimer's disease and amyotrophic lateral sclerosis. Here, we performed a meta-analysis of the literature of all the quantitative proteomic investigations of neuronal alterations in different models of Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis to distinguish between general and Parkinson's disease-specific pattern of neurodegeneration. Then, we merged proteomics data with genetics information from the DisGeNET database. The comparison of gene and protein information allowed us to identify 25 proteins involved uniquely in Parkinson's disease and we verified the alteration of one of them, i.e., transaldolase 1 (TALDO1), in the substantia nigra of 5 patients. By using open-source bioinformatics tools, we identified the biological processes specifically affected in Parkinson's disease, i.e., proteolysis, mitochondrion organization, and mitophagy. Eventually, we highlighted four cellular component complexes mostly involved in the pathogenesis: the proteasome complex, the protein phosphatase 2A, the chaperonins CCT complex, and the complex III of the respiratory chain.
神经退行性疾病的特征是中枢神经系统特定区域中特定神经元的进行性丧失。主要临床表现（运动障碍、认知障碍和/或精神障碍）取决于主要受影响的神经元群体。帕金森病是一种常见的运动障碍，其病因仍大多未知。黑质中多巴胺能神经元的进行性丧失导致运动控制受损。导致这些神经元进行性恶化的一些发病机制并非帕金森病所特有，而是与其他神经退行性疾病（如阿尔茨海默病和肌萎缩侧索硬化症）共享。在这里，我们对所有帕金森病、阿尔茨海默病和肌萎缩侧索硬化症不同模型中神经元变化的定量蛋白质组学研究的文献进行了荟萃分析，以区分一般和帕金森病特异性的神经退行性变模式。然后，我们将蛋白质组学数据与 DisGeNET 数据库中的遗传学信息合并。基因和蛋白质信息的比较使我们能够识别出 25 种仅与帕金森病相关的蛋白质，并且我们验证了其中一种蛋白质，即转醛醇酶 1（TALDO1）在 5 名患者的黑质中的改变。通过使用开源生物信息学工具，我们确定了帕金森病中特定受影响的生物学过程，即蛋白酶体、线粒体组织和线粒体自噬。最终，我们强调了四个主要涉及发病机制的细胞成分复合物：蛋白酶体复合物、蛋白磷酸酶 2A、伴侣蛋白 CCT 复合物和呼吸链复合物 III。
