Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide highly expressed in the central and peripheral nervous system, where it exerts several neuromodulatory functions and is an important trophic and protective factor. PACAP has been shown to activate several protective pathways, mainly through its specific PAC1 receptor and protein kinase A, C and MAP kinases downstream. It has been shown to have very potent neuroprotective actions against different neurotoxic agents both in vitro and in vivo. The aim of the present review is to provide an overview on the neurotoxic injuries against which PACAP exerts protection, and to give an insight into its protective mechanism. We give a summary of the neuroprotective effects against the most commonly used neurotoxic agents, such as 6-OHDA, MPTP, glutamate and some less well-known neurotoxic compounds. Also endogenous PACAP has neuroprotective effects, known from studies in PACAP knockout mice or from blocking endogenous effects by antagonists. Altogether, the vast amount of data for the neuroprotective effects of PACAP give a firm background for its endogenous role as part of the neuroprotective machinery and its possible future therapeutic use as a neuroprotective factor.

垂体腺苷酸环化酶激活多肽（PACAP）是在中枢和外周神经系统中高度表达的神经肽，在其中发挥多种神经调节功能，并且是重要的营养和保护因子。已显示PACAP主要通过其特定的PAC1受体以及下游的蛋白激酶A，C和MAP激酶激活多种保护途径。已经显示出在体外和体内对不同的神经毒性剂具有非常有效的神经保护作用。本综述的目的是概述PACAP对神经毒性损伤的保护作用，并深入了解其保护机制。我们总结了针对最常用的神经毒性剂（例如6-OHDA，MPTP，谷氨酸和一些鲜为人知的神经毒性化合物。内源性PACAP还具有神经保护作用，这从PACAP基因敲除小鼠的研究或通过拮抗剂阻断内源性作用中可知。总之，有关PACAP的神经保护作用的大量数据为其作为神经保护机制一部分的内源性作用及其作为神经保护因子的未来治疗用途提供了坚实的背景。