Abstract：
:Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophin. However, its role in human Alzheimer's disease (AD) is largely unknown. We examined PACAP expression in postmortem human AD and triple transgenic mouse (3xTG, Psen1/APPSwe/TauP301L) brains. We established an in vitro model of primary neuronal cell culture to study the protective effects of PACAP against β-amyloid (Aβ) toxicity. We further studied the PACAP-Sirtuin 3 (Sirt3) pathway on mitochondrial function. PACAP expression was reduced in AD and 3xTG mouse brains. This reduction was inversely correlated with Aβ and tau protein levels. Treatment with PACAP effectively protected neurons against Aβ toxicity. PACAP stimulated mitochondrial Sirt3 production. Similar to PACAP, Sirt3 was reduced in AD and 3xTG brains. Knocking down Sirt3 compromised the neuroprotective effects of PACAP, and this was reversed by over-expressing Sirt3. PACAP is reduced in AD and may represent a novel therapeutic strategy.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Han P,Tang Z,Yin J,Maalouf M,Beach TG,Reiman EM,Shi Jdoi
10.1016/j.neurobiolaging.2014.03.022subject
Has Abstractpub_date
2014-09-01 00:00:00pages
2064-71issue
9eissn
0197-4580issn
1558-1497pii
S0197-4580(14)00276-0journal_volume
35pub_type
杂志文章abstract：:We obtained serum samples and measured alpha 1-antichymotrypsin (ACT) levels in 36 pairs of consecutive probable Alzheimer's disease (AD) patients and age- and sex-matched, cognitively intact control subjects. Serum ACT was measured by radial immunodiffusion. Unique to this study, we found that ACT levels rose signifi...
journal_title：Neurobiology of aging
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更新日期：1994-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2019-07-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2006-12-01 00:00:00
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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更新日期：1997-09-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2014-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2012-12-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.02.012
更新日期：2019-06-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2020-09-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.03.004
更新日期：2015-06-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(88)80102-7
更新日期：1988-09-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00169-x
更新日期：2000-09-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2019-06-01 00:00:00
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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doi：10.1016/j.neurobiolaging.2008.02.017
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：1995-11-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2019-06-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.12.015
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journal_title：Neurobiology of aging
pub_type： 杂志文章,meta分析
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更新日期：2020-02-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00234-2
更新日期：2001-07-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.07.001
更新日期：2012-12-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.05.023
更新日期：2010-04-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
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更新日期：1999-09-01 00:00:00
abstract：:The mechanism by which amyloid beta (Aβ) causes neuronal dysfunction and/or death in Alzheimer's disease (AD) is unclear. Previously, we showed that Aβ inhibits several microtubule-dependent kinesin motors essential for mitosis and also present in mature neurons. Here, we show that inhibition of kinesin 5 (Eg5) by Aβ ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.02.006
更新日期：2014-08-01 00:00:00
