Readily Releasable Stores of Calcium in Neuronal Endolysosomes: Physiological and Pathophysiological Relevance.
Readily Releasable Stores of Calcium in Neuronal Endolysosomes: Physiological and Pathophysiological Relevance.
复制标题
神经元内溶酶体中容易释放的钙储存：生理学和病理生理学相关性。
DOI：
10.1007/978-3-030-12457-1_27
复制
发表时间：
2020
影响因子：
--
通讯作者：
Geiger,JonathanD
中科院分区：
文献类型：
--
作者：
Lakpa,KoffiL;Halcrow,PeterW;Chen,Xuesong;Geiger,JonathanD
神经元是长寿的有丝分裂后细胞，拥有复杂的内体和溶酶体系统（内溶酶体），用于蛋白质质量控制。最近，人们认识到内溶酶体含有高浓度（400–600 μM）易于释放的钙。这种酸性细胞器储存的钙释放有助于对神经元具有基本生理重要性的钙依赖性过程，包括神经递质释放、膜兴奋性、神经突生长、突触重塑和细胞活力。病理学上，内溶酶体结构和/或功能的紊乱在多种神经退行性疾病中被发现，包括阿尔茨海默病（AD）和 HIV-1 相关神经认知障碍（HAND）。并且，细胞内钙的失调与这些相同神经系统疾病的神经发病机制有关。因此，更好地了解钙从内溶酶体释放的机制以及这种释放对细胞器间信号传导、神经元的生理功能和可能的病理后果的影响非常重要。这样做可能会促进新的治疗方式的发展。
Neurons are long-lived post-mitotic cells that possess an elaborate system of endosomes and lysosomes (endolysosomes) for protein quality control. Relatively recently, endolysosomes were recognized to contain high concentrations (400–600 μM) of readily releasable calcium. The release of calcium from this acidic organelle store contributes to calcium-dependent processes of fundamental physiological importance to neurons including neurotransmitter release, membrane excitability, neurite outgrowth, synaptic remodeling, and cell viability. Pathologically, disturbances of endolysosome structure and/or function have been noted in a variety of neurodegenerative disorders including Alzheimer’s disease (AD) and HIV-1 associated neurocognitive disorder (HAND). And, dysregulation of intracellular calcium has been implicated in the neuropathogenesis of these same neurological disorders. Thus, it is important to better understand mechanisms by which calcium is released from endolysosomes as well as the consequences of such release to inter-organellar signaling, physiological functions of neurons, and possible pathological consequences. In doing so, a path forward towards new therapeutic modalities might be facilitated.