Pituitary Adenylate Cyclase-Activating Polypeptide Protects Against Beta-Amyloid Toxicity
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 Î²-amyloid (AÎ²) 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 AÎ² and tau protein levels. Treatment with PACAP effectively protected neurons against AÎ² 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.
Medical Subject Headings
Neurobiology of Aging
Digital Object Identifier (DOI)
Han, Pengcheng; Tang, Zhiwei; Yin, Junxiang; Maalouf, Marwan; Beach, Thomas G.; Reiman, Eric M.; and Shi, Jiong, "Pituitary Adenylate Cyclase-Activating Polypeptide Protects Against Beta-Amyloid Toxicity" (2014). Neurology. 189.