TY - JOUR
T1 - The mitochondrial impairment, oxidative stress and neurodegeneration connection
T2 - reality or just an attractive hypothesis?
AU - Fukui, Hirokazu
AU - Moraes, Carlos T.
N1 - Funding Information:
We are grateful to Giovanni Manfredi (Cornell University) for suggestions. Our work was supported by U.S. Public Health Service grants NS41777, EY10804 and CA085700, the Muscular Dystrophy Association and by the University of Miami Neuroscience Center. H.F. was supported by a Lois Pope LIFE Fellowship. The authors declare no conflict of interest.
PY - 2008/5
Y1 - 2008/5
N2 - Aging is the most important risk factor for common neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Aging in the central nervous system has been associated with elevated mutation load in mitochondrial DNA, defects in mitochondrial respiration and increased oxidative damage. These observations support a 'vicious cycle' theory which states that there is a feedback mechanism connecting these events in aging and age-associated neurodegeneration. Despite being an extremely attractive hypothesis, the bulk of the evidence supporting the mitochondrial vicious cycle model comes from pharmacological experiments in which the modes of mitochondrial enzyme inhibition are far from those observed in real life. Furthermore, recent in vivo evidence does not support this model. In this review, we focus on the relationship among the components of the putative vicious cycle, with particular emphasis on the role of mitochondrial defects on oxidative stress.
AB - Aging is the most important risk factor for common neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Aging in the central nervous system has been associated with elevated mutation load in mitochondrial DNA, defects in mitochondrial respiration and increased oxidative damage. These observations support a 'vicious cycle' theory which states that there is a feedback mechanism connecting these events in aging and age-associated neurodegeneration. Despite being an extremely attractive hypothesis, the bulk of the evidence supporting the mitochondrial vicious cycle model comes from pharmacological experiments in which the modes of mitochondrial enzyme inhibition are far from those observed in real life. Furthermore, recent in vivo evidence does not support this model. In this review, we focus on the relationship among the components of the putative vicious cycle, with particular emphasis on the role of mitochondrial defects on oxidative stress.
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U2 - 10.1016/j.tins.2008.02.008
DO - 10.1016/j.tins.2008.02.008
M3 - Review article
C2 - 18403030
AN - SCOPUS:42749087763
VL - 31
SP - 251
EP - 256
JO - Trends in Neurosciences
JF - Trends in Neurosciences
SN - 0378-5912
IS - 5
ER -