Raina Arun K, Hochman Ayala, Ickes Harold, Zhu Xiongwei, Ogawa Osamu, Cash Adam D, Shimohama Shun, Perry George, Smith Mark A
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, 44106, Cleveland, OH, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2003 Apr;27(2):251-4. doi: 10.1016/S0278-5846(03)00020-4.
A spectrum of apoptotic mediators are seen in neurons that are vulnerable in Alzheimer's disease (AD), leading many investigators to suggest that neuronal death in AD is mediated by an apoptotic process. Indeed, the environment of the AD brain is awash with proapoptotic mediators including amyloid-beta, oxidative stress, hydroxynonenal oxidants and metabolic alterations with concomitant energy failures. However, the phenotype that defines the terminal events that are pathogonomic of apoptosis, such as chromatin condensation, apoptotic bodies and membrane blebbing, are not seen in AD. Therefore, we speculated that, although AD presents with a proapoptotic environment, apoptosis does not proceed to completion. In this regard, we found that while the initiator phases of apoptosis were engaged, this does not lead to the activation of the terminal commitment phase necessary for apoptotic cell death. In other words, in AD, there is a lack of effective apoptotic signal propagation to distal effectors. This is a novel phenomenon (which we term abortosis) that represents an inhibition of apoptosis at the postinitiator stage in neurons that survive in AD.
在阿尔茨海默病（AD）中易受损的神经元中可见一系列凋亡介质，这使得许多研究人员认为AD中的神经元死亡是由凋亡过程介导的。确实，AD脑环境中充满了促凋亡介质，包括β-淀粉样蛋白、氧化应激、羟基壬烯醛氧化剂以及伴随能量衰竭的代谢改变。然而，定义凋亡特征性终末事件的表型，如染色质浓缩、凋亡小体和细胞膜起泡，在AD中并未出现。因此，我们推测，尽管AD呈现出促凋亡环境，但凋亡并未完成。在这方面，我们发现虽然凋亡的起始阶段已启动，但这并未导致凋亡细胞死亡所需的终末决定性阶段的激活。换句话说，在AD中，缺乏有效的凋亡信号向远端效应器的传播。这是一种新现象（我们称之为“流产凋亡”），它代表了在AD中存活的神经元中凋亡在起始后阶段受到抑制。
