Role of mitochondria in mutant SOD1 linked amyotrophic lateral sclerosis.
Publication/Presentation Date
8-1-2014
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an adult onset characterized by loss of both upper and lower motor neurons. In ~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.
Volume
1842
Issue
8
First Page
1295
Last Page
1301
ISSN
0006-3002
Published In/Presented At
Tan, W., Pasinelli, P., & Trotti, D. (2014). Role of mitochondria in mutant SOD1 linked amyotrophic lateral sclerosis. Biochimica et biophysica acta, 1842(8), 1295–1301. https://doi.org/10.1016/j.bbadis.2014.02.009
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
24568860
Department(s)
Administration and Leadership
Document Type
Article