Consequences of inhibiting amyloid precursor protein processing enzymes on synaptic function and plasticity.
Consequences of inhibiting amyloid precursor protein processing enzymes on synaptic function and plasticity.
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DOI：
10.1155/2012/272374
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发表时间：
2012
影响因子：
3.1
通讯作者：
Lee HK
中科院分区：
文献类型：
--
作者：
Wang H;Megill A;He K;Kirkwood A;Lee HK
Alzheimer's disease (AD) is a neurodegenerative disease, one of whose major pathological hallmarks is the accumulation of amyloid plaques comprised of aggregated β-amyloid (Aβ) peptides. It is now recognized that soluble Aβ oligomers may lead to synaptic dysfunctions early in AD pathology preceding plaque deposition. Aβ is produced by a sequential cleavage of amyloid precursor protein (APP) by the activity of β- and γ-secretases, which have been identified as major candidate therapeutic targets of AD. This paper focuses on how Aβ alters synaptic function and the functional consequences of inhibiting the activity of the two secretases responsible for Aβ generation. Abnormalities in synaptic function resulting from the absence or inhibition of the Aβ-producing enzymes suggest that Aβ itself may have normal physiological functions which are disrupted by abnormal accumulation of Aβ during AD pathology. This interpretation suggests that AD therapeutics targeting the β- and γ-secretases should be developed to restore normal levels of Aβ or combined with measures to circumvent the associated synaptic dysfunction(s) in order to have minimal impact on normal synaptic function.
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影响因子：
6.1
作者：
Almeida, CG;Tampellini, D;Gouras, GK
通讯作者：
Gouras, GK
影响因子：
56.9
作者：
Cao, XW;Südhof, TC
通讯作者：
Südhof, TC
DOI：
10.1073/pnas.93.24.13453
发表时间：
1996-11-26
影响因子：
11.1
作者：
Bear, MF
通讯作者：
Bear, MF
影响因子：
5.5
作者：
BLISS, TVP;LOMO, T
通讯作者：
LOMO, T
DOI：
10.1073/pnas.93.24.13445
发表时间：
1996-11-26
影响因子：
11.1
作者：
Bailey, CH;Bartsch, D;Kandel, ER
通讯作者：
Kandel, ER