Wainaina Moses N, Chen Zhichun, Zhong Chunjiu
Department of Neurology, Zhongshan Hospital; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.
Neurosci Bull. 2014 Apr;30(2):253-70. doi: 10.1007/s12264-013-1425-9. Epub 2014 Mar 24.
Late-onset Alzheimer's disease (LOAD) is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.
晚发性阿尔茨海默病（LOAD）是一种与年龄相关的神经退行性疾病，其特征是突触和神经元逐渐丧失，但其发病机制仍有待阐明。神经元存在于由神经元自身和神经胶质细胞构成的环境中。在本综述中，我们提出AD大脑中的神经元变性部分是由多种环境因素引起的。我们首先讨论各种环境应激及其在不同水平上的相应反应。然后，我们提出了一些特定病理变化的潜在机制，特别是全身水平的下丘脑-垂体-肾上腺轴功能障碍；细胞间水平的脑血管功能障碍、金属毒性、神经胶质细胞激活和Aβ毒性；以及细胞内水平的激酶-磷酸酶失衡和表观遗传修饰。最后，我们从环境应激的角度讨论了开发预防和治疗LOAD新策略的可能性。我们得出结论，环境因素通过多种病理机制在LOAD的发展中起重要作用。
