Teng Chih-Chung, Yang Ya-Ting, Chen Yu-Chi, Kuo Yu-Min, Sze Chun-I
Institute of Basic Medicine Science, National Cheng Kung University, Tainan, Taiwan, 70101, Republic of China.
Front Biosci (Elite Ed). 2012 Jan 1;4(5):1951-65. doi: 10.2741/e516.
Alzheimer's disease (AD) is the most common form of dementia with a progressive course. AD pathology is a manifestation of the underlying severity and neuroanatomic involvement of specific vulnerable brain regions and circuits that are responsible for neuronal dysfunction and death. The etiology of AD is largely unknown. It has been hypothesized that multiple factors, including genetic components, oxidative stress, intracellular or extracellular accumulation of amyloid, dysfunction of cystoskeletal and synapse components, neuronal loss by apoptosis, neuronal excitotoxicity, inflammation, mitochondria dysfunction, etc., may play important roles in the onset of the disease. WWOX/WOX1 is a candidate tumor suppressor. Human WWOX gene, encoding the WW domain-containing oxidoreductase (designated WWOX, FOR, or WOX1) protein, has been mapped to a fragile site on the chromosome ch16q23.3-24.1. Functionally, the WW domain is not only a tumor suppressor, but also a participant in molecular interactions, signaling, and apoptosis in many diseases. In this article, we review the potential mechanism by which WWOX/WOX1 may participate in the pathogenesis of AD with a focus on cell death signaling pathways in neurons.
阿尔茨海默病（AD）是最常见的一种具有进行性病程的痴呆症。AD病理学是特定易损脑区和神经回路潜在严重程度及神经解剖学受累情况的一种表现，这些脑区和神经回路负责神经元功能障碍和死亡。AD的病因很大程度上尚不清楚。据推测，多种因素，包括遗传成分、氧化应激、淀粉样蛋白在细胞内或细胞外的积累、细胞骨架和突触成分功能障碍、细胞凋亡导致的神经元丧失、神经元兴奋性毒性、炎症、线粒体功能障碍等，可能在该疾病的发病过程中起重要作用。WWOX/WOX1是一种候选肿瘤抑制因子。人类WWOX基因编码含WW结构域的氧化还原酶（命名为WWOX、FOR或WOX1）蛋白，已被定位到染色体16q23.3 - 24.1上的一个脆性位点。在功能上，WW结构域不仅是一种肿瘤抑制因子，而且在许多疾病的分子相互作用、信号传导和细胞凋亡中也发挥作用。在本文中，我们综述了WWOX/WOX1可能参与AD发病机制的潜在机制，重点关注神经元中的细胞死亡信号通路。
