TY - JOUR
T1 - Amyloid beta, mitochondrial dysfunction and synaptic damage
T2 - implications for cognitive decline in aging and Alzheimer's disease
AU - Reddy, P. Hemachandra
AU - Beal, M. Flint
N1 - Funding Information:
Our sincere apologies to all whose work could not be cited owing to space restrictions. This article is supported by grants from KaloBios Pharmaceuticals, Inc. and the National Institutes of Health (AG028072 and AG026051).
PY - 2008/2
Y1 - 2008/2
N2 - Recent studies of postmortem brains from Alzheimer's disease (AD) patients and transgenic mouse models of AD suggest that oxidative damage, induced by amyloid β (Aβ), is associated with mitochondria early in AD progression. Aβ and amyloid-precursor protein are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron-transport chain, increase reactive oxygen species production, cause mitochondrial damage and prevent neurons from functioning normally. Furthermore, accumulation of Aβ at synaptic terminals might contribute to synaptic damage and cognitive decline in patients with AD. Here, we describe recent studies regarding the roles of Aβ and mitochondrial function in AD progression and particularly in synaptic damage and cognitive decline.
AB - Recent studies of postmortem brains from Alzheimer's disease (AD) patients and transgenic mouse models of AD suggest that oxidative damage, induced by amyloid β (Aβ), is associated with mitochondria early in AD progression. Aβ and amyloid-precursor protein are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron-transport chain, increase reactive oxygen species production, cause mitochondrial damage and prevent neurons from functioning normally. Furthermore, accumulation of Aβ at synaptic terminals might contribute to synaptic damage and cognitive decline in patients with AD. Here, we describe recent studies regarding the roles of Aβ and mitochondrial function in AD progression and particularly in synaptic damage and cognitive decline.
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U2 - 10.1016/j.molmed.2007.12.002
DO - 10.1016/j.molmed.2007.12.002
M3 - Article
C2 - 18218341
AN - SCOPUS:39149122810
SN - 1471-4914
VL - 14
SP - 45
EP - 53
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
IS - 2
ER -