Title

Pituitary Adenylate Cyclase-Activating Polypeptide Protects Against Beta-Amyloid Toxicity

Department

neurology

Document Type

Article

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 invitro 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. © 2014 Elsevier Inc.

Medical Subject Headings

neurology

Publication Date

2014

Publication Title

Neurobiology of Aging

ISSN

1974580

Volume

35

Issue

9

First Page

2064

Last Page

2071

Digital Object Identifier (DOI)

10.1016/j.neurobiolaging.2014.03.022

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