Pituitary adenylate cyclase-activating polypeptide protects against β-amyloid toxicity

被引：95

作者：

Han, Pengcheng ^{[1
,2
]}

Tang, Zhiwei ^{[1
,2
,3
]}

Yin, Junxiang ^{[1
,2
]}

Maalouf, Marwan ^{[1
,2
]}

Beach, Thomas G. ^{[4
]}

Reiman, Eric M. ^{[5
]}

Shi, Jiong ^{[1
,2
]}

机构：

[1] St Joseph Hosp, Barrow Neurol Inst, NRC428, Dept Neurol, Phoenix, AZ 85013 USA

[2] Dign Hlth Org, Med Ctr, Phoenix, AZ 85013 USA

[3] Kunming Med Univ, Hosp 1, Dept Neurosurg, Kunmming, Peoples R China

[4] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA

[5] Banner Alzheimers Inst, Phoenix, AZ USA

来源：

NEUROBIOLOGY OF AGING | 2014年 / 35卷 / 09期

关键词：

Alzheimer's disease; PACAP; SIRT3; Mitochondrial respiration; CEREBELLAR GRANULE NEURONS; COMPLEX-I INHIBITOR; ALZHEIMERS-DISEASE; A-BETA; TAU PATHOLOGY; PC12; CELLS; PACAP; NEUROPEPTIDE; RECEPTORS; MODELS;

D O I：

10.1016/j.neurobiolaging.2014.03.022

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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 beta-amyloid (A beta) 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 A beta and tau protein levels. Treatment with PACAP effectively protected neurons against A beta 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. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：2064 / 2071

页数：8

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