Role of mitochondria in mutant SOD1 linked amyotrophic lateral sclerosis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Review

Tan, Wenzhi¹  Pasinelli, Piera¹  Trotti, Davide¹ 

[1] Thomas Jefferson Univ, Farber Inst Neurosci, Dept Neurosci, Frances & Joseph Weinberg Unit ALS Res, Philadelphia, PA 19107 USA

关键词: Amyotrophic lateral sclerosis;    Mitochondria;    Oxidative stress;   

DOI  :  10.1016/j.bbadis.2014.02.009

来源: Elsevier

【 摘 要 】

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an adult onset characterized by loss of both upper and lower motor neurons. In similar to 10% of cases, patients developed ALS with an apparent genetic linkage (familial ALS or fALS). Approximately 20% of fALS displays mutations in the SOD1 gene encoding superoxide dismutase 1. There are many proposed cellular and molecular mechanisms among which, mitochondrial dysfunctions occur early, prior to symptoms occurrence. In this review, we modeled the effect of mutant SOD1 protein via the formation of a toxic complex with Bcl2 on mitochondrial bioenergetics. Furthermore, we discuss that the shutdown of ATP permeation through mitochondrial outer membrane could lead to both respiration inhibition and temporary mitochondrial hyperpolarization. Moreover, we reviewed mitochondrial calcium signaling, oxidative stress, fission and fusion, autophagy and apoptosis in mutant SOD1-linked ALS. Functional defects in mitochondria appear early before symptoms are manifested in ALS. Therefore, mitochondrial dysfunction is a promising therapeutic target in ALS. This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction, and Neurodegenerative Diseases. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

Free