TY - JOUR
T1 - Mitochondrial hyperactivity as a potential therapeutic target in Parkinson's disease.
AU - Mor, Danielle Emille
AU - Murphy, Coleen T.
PY - 2020/8/12
Y1 - 2020/8/12
N2 - Mitochondrial dysfunction is thought to contribute to neurodegeneration in Parkinson's disease (PD), yet the cellular events that lead to mitochondrial disruption remain unclear. Post-mortem studies of PD patient brains and the use of complex I inhibitors to model the disease previously suggested a reduction in mitochondrial activity as a causative factor in PD, but this may represent an endpoint in the disease process. In our recent studies, we identified a novel link between branched-chain amino acid metabolism and PD, and uncovered mitochondrial hyperactivity as a potential alternative mechanism of PD pathogenesis. Increased mitochondrial activity may occur in a subset of PD patients, or may be a more common early event that precedes the ultimate loss of mitochondrial function. Therefore, it may be that any imbalance in mitochondrial activity, either increased or decreased, could cause a loss of mitochondrial homeostasis that leads to disease. An effective therapeutic strategy may be to target specific imbalances in activity at selective stages of PD or in specific patients, with any efforts to reduce mitochondrial activity constituting a surprising new avenue for PD treatment.
AB - Mitochondrial dysfunction is thought to contribute to neurodegeneration in Parkinson's disease (PD), yet the cellular events that lead to mitochondrial disruption remain unclear. Post-mortem studies of PD patient brains and the use of complex I inhibitors to model the disease previously suggested a reduction in mitochondrial activity as a causative factor in PD, but this may represent an endpoint in the disease process. In our recent studies, we identified a novel link between branched-chain amino acid metabolism and PD, and uncovered mitochondrial hyperactivity as a potential alternative mechanism of PD pathogenesis. Increased mitochondrial activity may occur in a subset of PD patients, or may be a more common early event that precedes the ultimate loss of mitochondrial function. Therefore, it may be that any imbalance in mitochondrial activity, either increased or decreased, could cause a loss of mitochondrial homeostasis that leads to disease. An effective therapeutic strategy may be to target specific imbalances in activity at selective stages of PD or in specific patients, with any efforts to reduce mitochondrial activity constituting a surprising new avenue for PD treatment.
UR - https://europepmc.org/articles/PMC7653964
U2 - 10.1016/j.tma.2020.07.007
DO - 10.1016/j.tma.2020.07.007
M3 - Article
C2 - 33178902
SN - 2468-5011
VL - 4
SP - 117
EP - 120
JO - Translational Medicine of Aging
JF - Translational Medicine of Aging
ER -