Amylotrophic Lateral Sclerosis-Like Motor Impairment in Prion Diseases

作     者：Eden Yitna Teferedegn Dawit Tesfaye Eyualem Abebe Cemal Un 

作者机构：Department of Biology Molecular Biology Division Ege University Izmir Turkey Institute for Animal Science University of Bonn Bonn Germany Department of Natural Sciences Elizabeth City State University Elizabet City NC USA 

出 版 物：《Neuroscience & Medicine》 (神经系统科学与医药（英文）)

年 卷 期：2019年第10卷第1期

页      面：15-29页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Prion Super Oxide Dismutase-1 Amyotrophic Lateral Sclerosis Motor Neuron Diseases Interactomes 

摘      要：Neurodegenerative diseases are collective diseases that affect different parts of the brain with common or distinct disease phenotype. In almost all of the Prion diseases, motor impairments that are characterized by motor derangement, apathy, ataxia, and myoclonus are documented and again are shared by motor neuron diseases (MND). Proteins such as;B-Cell lymphoma 2 (BCL2), Copper chaperone for superoxide dismutase (CCS), Amyloid beta precursor protein (APP), Amyloid Precursor-Like Protein1/2 (APLP1/2), Catalase (CAT), and Stress induced phosphoprotein 1 (STIP1), are common interactomes of Prion and superoxide dismutase 1 (SOD1). Although there is no strong evidence to show the interaction of SOD1 and Prion, the implicated common interacting proteins indicate the potential bilateral interaction of those proteins in health and disease. For example, down-regulation of Heat shock protein A (HSPA5), a Prion interactome, increases accumulation of misfolded SOD1 leading to MND. Loss of Cu uptake function disturbs normal function of CCS. Over-expressed proteasome subunit alpha 3 (PSMA3) could fatigue its normal function of removing misfolded proteins. Studies showed the increase in CAT and lipid oxidation both in Prion-knocked out animal and in catalase deficiency cases. Up regulation, down regulation or direct interaction with their interactomes are predicted molecular mechanisms by which Prion and SOD exert their effect. The loss of protective function or the gain of a novel toxic property by the principal proteins is shared in Prion and MND. Thus, it might be possible to conclude that the interplay of proteins displayed in both diseases could be a key phenomenon in motor dysfunction development.