Role of PACAP in Ischemic Neural Death
Role of PACAP in Ischemic Neural Death
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DOI：
10.1007/s12031-008-9077-3
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发表时间：
2008-11-01
影响因子：
3.1
通讯作者：
Shioda, Seiji
中科院分区：
文献类型：
--
作者：
Ohtaki, Hirokazu;Nakamachi, Tomoya;Shioda, Seiji
垂体腺苷酸环化酶激活多肽 (PACAP) 是一种神经肽，于 1989 年首次从绵羊下丘脑中分离出来。自发现以来，已有 2,000 多篇论文报道了 PACAP 的组织和细胞分布及其功能意义。许多论文报道，即使在缺血诱导后数小时施用 PACAP，在啮齿类动物的整体和局灶性缺血后，PACAP（而不是血管活性肠肽）也能抑制神经元细胞死亡或减少梗塞体积。此外，最近使用 PACAP 基因缺陷小鼠的研究表明，与外源性施用 PACAP 类似，内源性 PACAP 也对神经保护有很大贡献。研究表明，PACAP 的神经保护可能会延长治疗缺血相关疾病（例如中风）的治疗时间窗。本综述总结了 PACAP 对缺血性神经细胞死亡的影响，并通过体内缺血研究阐明了其机制。此外，还综述了 PACAP 对损伤应激模型体外神经元和神经元样细胞培养物的缺血性神经保护作用的前瞻性机制。最后，讨论了用于人类治疗的 PACAP 和/或受体激动剂的开发。
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that was first isolated from an ovine hypothalamus in 1989. Since its discovery, more than 2,000 papers have reported on the tissue and cellular distribution and functional significance of PACAP. A number of papers have reported that PACAP but not the vasoactive intestinal peptide suppressed neuronal cell death or decreased infarct volume after global and focal ischemia in rodents, even if PACAP was administered several hours after ischemia induction. In addition, recent studies using PACAP gene-deficient mice demonstrated that endogenous PACAP also contributes greatly to neuroprotection similarly to exogenously administered PACAP. The studies suggest that neuroprotection by PACAP might extend the therapeutic time window for treatment of ischemia-related conditions, such as stroke. This review summarizes the effects of PACAP on ischemic neuronal cell death, and the mechanism clarified in vivo ischemic studies. In addition, the prospective mechanism of PACAP on ischemic neuroprotection from in vitro neuronal and neuronal-like cell cultures with injured stress model is reviewed. Finally, the development of PACAP and/or receptor agonists for human therapy is discussed.