Lim Dmitry, Ronco Virginia, Grolla Ambra A, Verkhratsky Alexei, Genazzani Armando A
Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Via Bovio 6, 28100, Novara, Italy.
Rev Physiol Biochem Pharmacol. 2014;167:45-65. doi: 10.1007/112_2014_19.
The most accredited (and fashionable) hypothesis of the pathogenesis of Alzheimer Disease (AD) sees accumulation of β-amyloid protein in the brain (in both soluble and insoluble forms) as a leading mechanism of neurotoxicity. How β-amyloid triggers the neurodegenerative disorder is at present unclear, but growing evidence suggests that a deregulation of Ca(2+) homeostasis and deficient Ca(2+) signalling may represent a fundamental pathogenic factor. Given that symptoms of AD are most likely linked to synaptic dysfunction (at the early stages) followed by neuronal loss (at later and terminal phases of the disease), the effects of β-amyloid have been mainly studied in neurones. Yet, it must be acknowledged that neuroglial cells, including astrocytes, contribute to pathological progression of most (if not all) neurological diseases. Here, we review the literature pertaining to changes in Ca(2+) signalling in astrocytes exposed to exogenous β-amyloid or in astrocytes from transgenic Alzheimer disease animals models, characterized by endogenous β-amyloidosis. Accumulated experimental data indicate deregulation of Ca(2+) homeostasis and signalling in astrocytes in AD, which should be given full pathogenetic consideration. Further studies are warranted to comprehend the role of deficient astroglial Ca(2+) signalling in the disease progression.
关于阿尔茨海默病（AD）发病机制，最受认可（且最为流行）的假说是，大脑中β-淀粉样蛋白（以可溶性和不可溶性两种形式）的积累是神经毒性的主要机制。目前尚不清楚β-淀粉样蛋白如何引发神经退行性疾病，但越来越多的证据表明，Ca(2+) 稳态失调和Ca(2+) 信号传导缺陷可能是一个基本的致病因素。鉴于AD的症状很可能与突触功能障碍（在疾病早期）相关，随后是神经元丢失（在疾病的后期和终末期），β-淀粉样蛋白的作用主要在神经元中进行了研究。然而，必须承认的是，包括星形胶质细胞在内的神经胶质细胞对大多数（如果不是全部）神经系统疾病的病理进展都有影响。在此，我们回顾了有关暴露于外源性β-淀粉样蛋白的星形胶质细胞或来自以内源性β-淀粉样变性为特征的转基因阿尔茨海默病动物模型的星形胶质细胞中Ca(2+) 信号变化的文献。积累的实验数据表明，AD中星形胶质细胞的Ca(2+) 稳态和信号传导失调，这在发病机制上应予以充分考虑。有必要进行进一步研究以了解星形胶质细胞Ca(2+) 信号传导缺陷在疾病进展中的作用。
