TY - JOUR
T1 - Mitochondrial Dysfunction in Neurodegenerative Diseases Associated with Copper Imbalance
AU - Rossi, Luisa
AU - Lombardo, Marco F.
AU - Ciriolo, Maria R.
AU - Rotilio, Giuseppe
PY - 2004/3
Y1 - 2004/3
N2 - Copper is an essential transition metal ion for the function of key metabolic enzymes, but its uncontrolled redox reactivity is source of reactive oxygen species. Therefore a network of transporters strictly controls the trafficking of copper in living systems. Deficit, excess, or aberrant coordination of copper are conditions that may be detrimental, especially for neuronal cells, which are particularly sensitive to oxidative stress. Indeed, the genetic disturbances of copper homeostasis, Menkes' and Wilson's diseases, are associated with neurodegeneration. Furthermore, copper interacts with the proteins that are the hallmarks of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion diseases, and familial amyotrophic lateral sclerosis. In all cases, copper-mediated oxidative stress is linked to mitochondrial dysfunction, which is a common feature of neurodegeneration. In particular we recently demonstrated that in copper deficiency, mitochondrial function is impaired due to decreased activity of cytochrome c oxidase, leading to production of reactive oxygen species, which in turn triggers mitochondria-mediated apoptotic neurodegeneration.
AB - Copper is an essential transition metal ion for the function of key metabolic enzymes, but its uncontrolled redox reactivity is source of reactive oxygen species. Therefore a network of transporters strictly controls the trafficking of copper in living systems. Deficit, excess, or aberrant coordination of copper are conditions that may be detrimental, especially for neuronal cells, which are particularly sensitive to oxidative stress. Indeed, the genetic disturbances of copper homeostasis, Menkes' and Wilson's diseases, are associated with neurodegeneration. Furthermore, copper interacts with the proteins that are the hallmarks of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion diseases, and familial amyotrophic lateral sclerosis. In all cases, copper-mediated oxidative stress is linked to mitochondrial dysfunction, which is a common feature of neurodegeneration. In particular we recently demonstrated that in copper deficiency, mitochondrial function is impaired due to decreased activity of cytochrome c oxidase, leading to production of reactive oxygen species, which in turn triggers mitochondria-mediated apoptotic neurodegeneration.
KW - Apoptosis
KW - Copper
KW - Cuproenzymes
KW - Mitochondria
KW - Neurodegeneration
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=1542287942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1542287942&partnerID=8YFLogxK
U2 - 10.1023/B:NERE.0000014820.99232.8a
DO - 10.1023/B:NERE.0000014820.99232.8a
M3 - Article
C2 - 15038597
AN - SCOPUS:1542287942
VL - 29
SP - 493
EP - 504
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 3
ER -