TY - JOUR
T1 - Mitochondrial defects in transgenic mice expressing Cu,Zn Superoxide Dismutase mutations, the role of Copper Chaperone for SOD1
AU - Son, Marjatta
AU - Elliott, Jeffrey L.
N1 - Funding Information:
This work was supported by grants from the NINDS ( R01 NS055315 ) and the Muscular Dystrophy Association (MDA) to Dr. Jeffrey L. Elliott.
PY - 2014/1/15
Y1 - 2014/1/15
N2 - Several hypotheses have been proposed for the mechanisms underlying mutant Cu,Zn Superoxide Dismutase-related Amyotrophic Lateral Sclerosis. These include aggregation pathology, mitochondrial dysfunctions, oxidative stress, and glutamate-mediated excitotoxicity. Mitochondrial disease may be a primary event in neurodegeneration, contributing to oxidative stress and apoptosis, or it may be caused by other cellular processes. Mitochondrial structural abnormalities have been detected in the skeletal muscle, lymphoblast and central nervous system of Amyotrophic Lateral Sclerosis patients. The cause or even the extent of mitochondrial defects in spinal cord and brain of patients with Cu,Zn Superoxide Dismutase mutations is difficult to determine because of rapid mitochondrial deterioration in autopsy samples. The focus of this review is how abnormalities in Cu,Zn Superoxide Dismutase redox states, folding and metallation contribute to mitochondrial deficiencies, investigating the differences in mitochondrial defects observed among transgenic mice expressing various Cu,Zn Superoxide Dismutase mutations.
AB - Several hypotheses have been proposed for the mechanisms underlying mutant Cu,Zn Superoxide Dismutase-related Amyotrophic Lateral Sclerosis. These include aggregation pathology, mitochondrial dysfunctions, oxidative stress, and glutamate-mediated excitotoxicity. Mitochondrial disease may be a primary event in neurodegeneration, contributing to oxidative stress and apoptosis, or it may be caused by other cellular processes. Mitochondrial structural abnormalities have been detected in the skeletal muscle, lymphoblast and central nervous system of Amyotrophic Lateral Sclerosis patients. The cause or even the extent of mitochondrial defects in spinal cord and brain of patients with Cu,Zn Superoxide Dismutase mutations is difficult to determine because of rapid mitochondrial deterioration in autopsy samples. The focus of this review is how abnormalities in Cu,Zn Superoxide Dismutase redox states, folding and metallation contribute to mitochondrial deficiencies, investigating the differences in mitochondrial defects observed among transgenic mice expressing various Cu,Zn Superoxide Dismutase mutations.
KW - Copper Chaperone for SOD1
KW - Cu,Zn Superoxide Dismutase
KW - Mitochondria
KW - Mutation
KW - Neurodegeneration
KW - Transgenic mouse
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U2 - 10.1016/j.jns.2013.11.004
DO - 10.1016/j.jns.2013.11.004
M3 - Review article
C2 - 24269091
AN - SCOPUS:84892615874
SN - 0022-510X
VL - 336
SP - 1
EP - 7
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -