TY - JOUR
T1 - Abnormal tau, mitochondrial dysfunction, impaired axonal transport of mitochondria, and synaptic deprivation in Alzheimer's disease
AU - Reddy, P. Hemachandra
N1 - Funding Information:
This research was supported by NIH grants AG028072 , RR00163 , and Alzheimer Association grant IIRG-09-92429 .
PY - 2011/9/30
Y1 - 2011/9/30
N2 - Growing evidence suggests that amyloid beta (Aβ) and tau pathologies are strongly associated with mitochondrial dysfunction and neuronal damage in Alzheimer's disease (AD). Extensive research of AD postmortem brains, mouse and fly models, including triple transgenic AD mice and mutant tau mice, and cell culture studies revealed that tau hyperphosphorylation is caused by multiple factors, including intraneuronal Aβ-oligomers, chronic oxidative stress, reduced insulin-like growth factor 1, and astrocytic mediated-Aβ and caspase activation. Overexpressed and phosphorylated tau appears to impair axonal transport of organelles causing synapse starvation, depletion of ATP, and ultimately neuronal damage. This article evaluates the role of tau in mitochondrial dysfunction and assesses how hyperphosphorylated tau impairs axonal transport of organelles in AD neurons.
AB - Growing evidence suggests that amyloid beta (Aβ) and tau pathologies are strongly associated with mitochondrial dysfunction and neuronal damage in Alzheimer's disease (AD). Extensive research of AD postmortem brains, mouse and fly models, including triple transgenic AD mice and mutant tau mice, and cell culture studies revealed that tau hyperphosphorylation is caused by multiple factors, including intraneuronal Aβ-oligomers, chronic oxidative stress, reduced insulin-like growth factor 1, and astrocytic mediated-Aβ and caspase activation. Overexpressed and phosphorylated tau appears to impair axonal transport of organelles causing synapse starvation, depletion of ATP, and ultimately neuronal damage. This article evaluates the role of tau in mitochondrial dysfunction and assesses how hyperphosphorylated tau impairs axonal transport of organelles in AD neurons.
KW - Alzheimer's disease
KW - Amyloid beta
KW - Axonal transport of mitochondria
KW - Hyperphosphorylation of tau
KW - Mitochondrial dysfunction
KW - Oxidative stress
KW - Triple transgenic mice
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U2 - 10.1016/j.brainres.2011.07.052
DO - 10.1016/j.brainres.2011.07.052
M3 - Review article
C2 - 21872849
AN - SCOPUS:80052846665
SN - 0006-8993
VL - 1415
SP - 136
EP - 148
JO - Brain research
JF - Brain research
ER -