Therapeutic potential of PACAP for neurodegenerative diseases

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is widely expressed in the central and peripheral nervous system. PACAP can initiate multiple signaling pathways through binding with three class B G-protein coupled receptors, PAC1, VPAC1 and VPAC2. Previous studies have revealed numerous biological activities of PACAP in the nervous system. PACAP acts as a neurotransmitter, neuromodulator and neurotrophic factor. Recently, its neuroprotective potential has been demonstrated in numerous in vitro and in vivo studies. Furthermore, evidence suggests that PACAP might move across the blood-brain barrier in amounts sufficient to affect the brain functions. Therefore, PACAP has been examined as a potential therapeutic method for neurodegenerative diseases. The present review summarizes the recent findings with special focus on the models of Alzheimer's disease (AD) and Parkinson's disease (PD). Based on these observations, the administered PACAP inhibits pathological processes in models of AD and PD, and alleviates clinical symptoms. It thus offers a novel therapeutic approach for the treatment of AD and PD.

PACAP deficiency as a model of aging

“…The protective effects of PACAP in models of neurodegenerative diseases have been widely documented and its effects in models of Parkinson's, Huntington's, and Alzheimer's diseases are known (Cabezas-Llobet et al 2018;Reglodi et al 2011Reglodi et al , 2017Yang et al 2015). However, in spite of these diseases characteristically appearing in older ages, most studies have been performed in young animals, which can yield misleading extrapolations to older age groups (Tamas et al 2005(Tamas et al , 2006.…”

gH625-liposomes as tool for pituitary adenylate cyclase-activating polypeptide brain delivery

“…PACAP is a member of the vasoactive intestinal peptide/secretin/growth hormone-releasing hormone/glucagon superfamily 43,44 . PACAP showed neuroprotective effects in neurodegeneration models of cerebral ischemia and brain injuries 41,44–49 and in other neurological diseases such as Parkinson’s disease 50–54 and Alzheimer’s disease 46,50,54–59 . Nevertheless, use of PACAP in clinical practice presents some limitations because of its low stability in human plasma 60 , rapid degradation 61 and peripheral actions 62–64 .…”

PACAP and PAC1R are differentially expressed in motor cortex of amyotrophic lateral sclerosis patients and support survival of iPSC‐derived motor neurons

“…PACAP is a pleiotropic molecule, involved in a wide range of physiological processes, including cell survival during neurodegenerative conditions, stress response and cell division (Canonico et al, ; Castorina et al, ; Castorina, Giunta, Mazzone, Cardile, & D'Agata, ; Castorina, Scuderi, D'Amico, Drago, & D'Agata, ; Cavallaro et al, , ; D'Agata & Cavallaro, ; D'Agata, Cavallaro, Stivala, Travali, & Canonico, ; D'Amico et al, , ; Giunta et al, ; Maino et al, ; Maugeri, D'Amico, & Gagliano, ; Maugeri, D'Amico, & Saccone, ; Scuderi et al, ). Moreover, it is known to act as a neurotransmitter and/or a neuromodulator in the peripheral and central nervous system (Jóźwiak‐Bębenista, Kowalczyk, & Nowak, ; Shioda et al, , ; Yang et al, ). Despite recent findings have revealed that PACAP is able to rescue rat motor neurons against glutamate‐induced excitotoxicity in vitro (Tomimatsu & Arakawa, ), and confers neuroprotection to central visceromotor neurons via autocrine pathways in SOD1(G93A) mice model (Ringer et al, ), the effect of PACAP in ALS still remains unknown.…”