Abstract：
:The alpha-secretase-derived form of the amyloid precursor protein (sAPPalpha), which is released from neurons in an activity-dependent manner, has been shown to promote long-term survival of hippocampal and cortical neurons in culture and can protect those neurons against excitotoxic and ischemic injury in culture and in vivo. The signal transduction pathway(s) activated by sAPPalpha has not been established. We now report that sAPPalpha activates the phosphatidylinositol-3-kinase (PI(3)K)-Akt kinase signaling pathway in cultured hippocampal neurons. sAPPalpha also stimulates phosphorylation of p42 (ERK1) and p44 (ERK2) mitogen-activated protein (MAP) kinases by a PI(3)K-independent pathway. Treatment of neurons with sAPPalpha protects them against death induced by trophic factor deprivation and exposure to glutamate, and these survival-promoting effects of sAPPalpha are abolished or attenuated when either PI(3)K or p42/p44 MAP kinases are selectively blocked. Exposure of neurons to sAPPalpha resulted in a decrease in the level of IkappaBbeta and an increase in NF-kappaB DNA binding activity, both of which were blocked by wortmannin, suggesting that the transcription factor NF-kappaB may be a downstream target of the PI(3)K-Akt pathway that may play a role in the cell survival-promoting action of sAPPalpha. These findings suggest that the PI(3)K-Akt pathway and p42/p44 MAP kinases mediate responses of neurons to sAPPalpha in physiological and pathological settings, with implications for synaptic plasticity and the pathogenesis of Alzheimer's disease.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Cheng G,Yu Z,Zhou D,Mattson MPdoi
10.1006/exnr.2002.7920keywords:
subject
Has Abstractpub_date
2002-06-01 00:00:00pages
407-14issue
2eissn
0014-4886issn
1090-2430pii
S0014488602979203journal_volume
175pub_type
杂志文章abstract：:The tibial functional index has been employed to assess functional recovery in rats following nerve repair by direct coaptation under tension or by grafting. Recovery after direct repair of small to moderate gap sizes was better than that after grafting. ...
journal_title：Experimental neurology
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journal_title：Experimental neurology
pub_type： 杂志文章
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journal_title：Experimental neurology
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journal_title：Experimental neurology
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journal_title：Experimental neurology
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