TY - JOUR
T1 - Redox regulation of protein misfolding, mitochondrial dysfunction, synaptic damage, and cell death in neurodegenerative diseases
AU - Nakamura, Tomohiro
AU - Cho, Dong Hyung
AU - Lipton, Stuart A.
PY - 2012/11
Y1 - 2012/11
N2 - The loss or injury of neurons associated with oxidative and nitrosative redox stress plays an important role in the onset of various neurodegenerative diseases. Specifically, nitric oxide (NO), can affect neuronal survival through a process called S-nitrosylation, by which the NO group undergoes a redox reaction with specific protein thiols. This in turn can lead to the accumulation of misfolded proteins, which generally form aggregates in Alzheimer's, Parkinson's, and other neurodegenerative diseases. Evidence suggests that S-nitrosylation can also impair mitochondrial function and lead to excessive fission of mitochondria and consequent bioenergetic compromise via effects on the activity of the fission protein dynamin-related protein 1 (Drp1). This insult leads to synaptic dysfunction and loss. Additionally, high levels of NO can S-nitrosylate a number of aberrant targets involved in neuronal survival pathways, including the antiapoptotic protein XIAP, inhibiting its ability to prevent apoptosis.
AB - The loss or injury of neurons associated with oxidative and nitrosative redox stress plays an important role in the onset of various neurodegenerative diseases. Specifically, nitric oxide (NO), can affect neuronal survival through a process called S-nitrosylation, by which the NO group undergoes a redox reaction with specific protein thiols. This in turn can lead to the accumulation of misfolded proteins, which generally form aggregates in Alzheimer's, Parkinson's, and other neurodegenerative diseases. Evidence suggests that S-nitrosylation can also impair mitochondrial function and lead to excessive fission of mitochondria and consequent bioenergetic compromise via effects on the activity of the fission protein dynamin-related protein 1 (Drp1). This insult leads to synaptic dysfunction and loss. Additionally, high levels of NO can S-nitrosylate a number of aberrant targets involved in neuronal survival pathways, including the antiapoptotic protein XIAP, inhibiting its ability to prevent apoptosis.
UR - http://www.scopus.com/inward/record.url?scp=84866540615&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2012.06.032
DO - 10.1016/j.expneurol.2012.06.032
M3 - Review article
C2 - 22771760
AN - SCOPUS:84866540615
SN - 0014-4886
VL - 238
SP - 12
EP - 21
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -