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星形胶质细胞中的钙信号传导工具包与阿尔茨海默病的时空进展

Calcium signalling toolkits in astrocytes and spatio-temporal progression of Alzheimer's disease.

作者信息

Lim Dmitry, Rodríguez-Arellano J J, Parpura Vladimir, Zorec Robert, Zeidán-Chuliá Fares, Genazzani Armando A, Verkhratsky Alexei

机构信息

Faculty of Life Sciences, The University of Manchester, Manchester, UK.

出版信息

Curr Alzheimer Res. 2016;13(4):359-69. doi: 10.2174/1567205013666151116130104.

Abstract

Pathological remodelling of astroglia represents an important component of the pathogenesis of Alzheimer's disease (AD). In AD astrocytes undergo both atrophy and reactivity; which may be specific for different stages of the disease evolution. Astroglial reactivity represents the generic defensive mechanism, and inhibition of astrogliotic response exacerbates b-amyloid pathology associated with AD. In animal models of AD astroglial reactivity is different in different brain regions, and the deficits of reactive response observed in entorhinal and prefrontal cortices may be linked to their vulnerability to AD progression. Reactive astrogliosis is linked to astroglial Ca(2+) signalling, this latter being widely regarded as a mechanism of astroglial excitability. The AD pathology evolving in animal models as well as acute or chronic exposure to β-amyloid induce pathological remodelling of Ca(2+) signalling toolkit in astrocytes. This remodelling modifies astroglial Ca(2+) signalling and may be linked to cellular mechanisms of AD pathogenesis.

摘要

星形胶质细胞的病理性重塑是阿尔茨海默病(AD)发病机制的重要组成部分。在AD中,星形胶质细胞会发生萎缩和反应性改变,这可能在疾病发展的不同阶段具有特异性。星形胶质细胞的反应性是一种普遍的防御机制,抑制星形胶质细胞反应会加剧与AD相关的β-淀粉样蛋白病理改变。在AD动物模型中,不同脑区的星形胶质细胞反应性不同,在内嗅皮质和前额叶皮质观察到的反应性反应缺陷可能与其对AD进展的易感性有关。反应性星形胶质细胞增生与星形胶质细胞Ca(2+)信号传导有关,后者被广泛认为是星形胶质细胞兴奋性的一种机制。在动物模型中演变的AD病理以及急性或慢性暴露于β-淀粉样蛋白会诱导星形胶质细胞中Ca(2+)信号传导工具包的病理性重塑。这种重塑改变了星形胶质细胞Ca(2+)信号传导,可能与AD发病机制的细胞机制有关。

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