Mitochondrial dysfunction in amyotrophic lateral sclerosis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1802

Review

Shi, Ping²  Gal, Jozsef¹  Kwinter, David M.¹  Liu, Xiaoyan¹  Zhu, Haining^1,2 

[1] Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40506 USA

[2] Univ Kentucky, Coll Med, Grad Ctr Toxicol, Lexington, KY 40506 USA

关键词: Amyotrophic lateral sclerosis;    Mutant SOD1;    Mitochondrial function;    Axonal transport;    Mitochondrial dynamics;   

DOI  :  10.1016/j.bbadis.2009.08.012

来源: Elsevier

【 摘 要 】

The etiology of motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remains to be better understood. Based on the studies from ALS patients and transgenic animal models, it is believed that ALS is likely to be a multifactorial and multisystem disease. Many mechanisms have been postulated to be involved in the pathology of ALS, such as oxidative stress, glutamate excitotoxicity, mitochondrial damage, defective axonal transport, glia cell pathology and aberrant RNA metabolism. Mitochondria, which play crucial roles in excitotoxicity, apoptosis and cell survival, have shown to be an early target in ALS pathogenesis and contribute to the disease progression. Morphological and functional defects in mitochondria were found in both human patients and ALS mice overexpressing mutant SOD1. Mutant SOD1 was found to be preferentially associated with mitochondria and subsequently impair mitochondrial function. Recent studies suggest that axonal transport of mitochondria along microtubules and mitochondrial dynamics may also be disrupted in ALS. These results also illustrate the critical importance of maintaining proper mitochondrial function in axons and neuromuscular junctions, supporting the emerging dying-back axonopathy model of ALS. In this review, we will discuss how mitochondrial dysfunction has been linked to the ALS variants of SOD1 and the mechanisms by which mitochondrial damage contributes to the disease etiology. (C) 2009 Elsevier B.V. All rights reserved.

【 授权许可】

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