Inhibitory Effect of PACAP on Caspase Activity in Neuronal Apoptosis: A Better Understanding Towards Therapeutic Applications in Neurodegenerative Diseases
Inhibitory Effect of PACAP on Caspase Activity in Neuronal Apoptosis: A Better Understanding Towards Therapeutic Applications in Neurodegenerative Diseases
复制标题
DOI：
10.1007/s12031-008-9087-1
复制
发表时间：
2008-11-01
影响因子：
3.1
通讯作者：
Vaudry, David
中科院分区：
文献类型：
--
作者：
Dejda, Agnieszka;Jolivel, Valerie;Vaudry, David
程序性细胞死亡是中枢神经系统正常发育的一部分，也与各种神经退行性疾病有关。半胱氨酸依赖的天冬氨酸特异性蛋白水解酶(Caspase)在导致细胞凋亡的一系列事件中起着关键作用。现在已经确定了许多抑制细胞死亡的因素，但其潜在的机制还不完全清楚。研究表明，垂体腺苷环化酶激活多肽(PACAP)在发育过程中具有神经营养活性，并能防止缺血等各种损伤诱导的神经元凋亡。PACAP的大部分神经保护作用是通过PAC1受体介导的。该受体激活第二信使的转导级联反应，刺激Bcl2的表达，从而抑制细胞色素c的释放，并阻断caspase的激活。PACAP对细胞凋亡级联反应的抑制作用表明，选择性、稳定和有效的PACAP衍生物可能在治疗创伤后和/或慢性神经变性过程中具有潜在的治疗价值。
Programmed cell death, which is part of the normal development of the central nervous system, is also implicated in various neurodegenerative disorders. Cysteine-dependent aspartate-specific proteases (caspases) play a pivotal role in the cascade of events leading to apoptosis. Many factors that inhibit cell death have now been identified, but the underlying mechanisms are not fully understood. Pituitary adenylate cylase-activating polypeptide (PACAP) has been shown to exert neurotrophic activities during development and to prevent neuronal apoptosis induced by various insults such as ischemia. Most of the neuroprotective effects of PACAP are mediated through the PAC1 receptor. This receptor activates a transduction cascade of second messengers to stimulate Bcl-2 expression, which inhibits cytochrome c release and blocks the activation of caspases. The inhibitory effect of PACAP on the apoptotic cascade suggests that selective, stable, and potent PACAP derivatives could potentially be of therapeutic value for the treatment of post-traumatic and/or chronic neurodegenerative processes.