Mitochondrial Calcium Signaling as a Therapeutic Target for Alzheimer’s Disease

doi:10.2174/1567205016666191210091302
摘要

线粒体通过消耗呼吸过程中产生的电化学梯度来吸收钙(Ca2+)。Ca2+内流到线粒体基质中有助于维持代谢功能，并导致细胞内Ca2+信号转导过程中细胞内Ca2+的增加。线粒体Ca2+稳态受到位于内外线粒体膜的蛋白质和内质网Ca2+信号的交叉调控。越来越多的证据表明线粒体Ca2+超载是一种与阿尔茨海默病(AD)相关的病理表型。由于在AD的典型病理特征出现之前就可以观察到细胞内Ca2+的失调，我们认为线粒体Ca2+超载也可能在AD的病因学中发挥重要作用。高线粒体Ca2+摄取容易损害神经元功能，并通过损害线粒体呼吸，增加活性氧的形成和诱导细胞凋亡而恶化AD进展。此外，线粒体Ca2+超载可通过线粒体自噬破坏线粒体循环。这篇综述将讨论参与线粒体Ca2+失调的分子角色和针对这种失调的药物治疗。由于目前大多数AD疗法是基于淀粉病、tauopathy和胆碱能假说，它们只能缓解症状。因此，确定如何重建线粒体Ca2+稳态可能有助于开发新的AD治疗干预。
关键词: 钙
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DOI https://dx.doi.org/10.2174/1567205016666191210091302	Print ISSN 1567-2050
Publisher Name Bentham Science Publisher	Online ISSN 1875-5828
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