Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, 34854 Maltepe, Istanbul, Turkey.
Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, 34854 Maltepe, Istanbul, Turkey.
Free Radic Biol Med. 2015 Nov;88(Pt A):42-50. doi: 10.1016/j.freeradbiomed.2015.05.038. Epub 2015 Jun 12.
Protein processing including folding, unfolding and degradation is involved in the mechanisms of many diseases. Unfolded protein response and/or endoplasmic reticulum stress are accepted to be the first steps which should be completed via protein degradation. In this direction, proteasomal system and autophagy play important role as the degradation pathways and controlled via complex mechanisms. Amyotrophic lateral sclerosis is a multifactorial neurodegenerative disease which is also known as the most catastrophic one. Mutation of many different genes are involved in the pathogenesis such as superoxide dismutase 1, chromosome 9 open reading frame 72 and ubiquilin 2. These genes are mainly related to the antioxidant defense systems, endoplasmic reticulum stress related proteins and also protein aggregation, degradation pathways and therefore mutation of these genes cause related disorders.This review focused on the role of protein processing via endoplasmic reticulum and proteasomal system in amyotrophic lateral sclerosis which are the main players in the pathology. In this direction, dysfunction of endoplasmic reticulum associated degradation and related cell death mechanisms that are autophagy/apoptosis have been detailed.
蛋白质的加工包括折叠、展开和降解，涉及许多疾病的机制。未折叠蛋白反应和/或内质网应激被认为是通过蛋白质降解完成的第一步。在这方面，蛋白酶体系统和自噬作为降解途径发挥着重要作用，并通过复杂的机制进行控制。肌萎缩侧索硬化症是一种多因素神经退行性疾病，也被称为最具灾难性的疾病。许多不同基因的突变参与了发病机制，如超氧化物歧化酶 1、9 号染色体开放阅读框 72 和泛素 2。这些基因主要与抗氧化防御系统、内质网应激相关蛋白以及蛋白质聚集、降解途径有关，因此这些基因的突变导致相关疾病。本综述重点关注通过内质网和蛋白酶体系统在肌萎缩侧索硬化症中的作用，这两个系统是病理学中的主要参与者。在这方面，详细描述了内质网相关降解的功能障碍和相关的细胞死亡机制，即自噬/细胞凋亡。
