Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA.
Adv Exp Med Biol. 2020;1131:681-697. doi: 10.1007/978-3-030-12457-1_27.
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.
神经元是长寿命的有丝分裂后细胞，具有复杂的内体和溶酶体（内溶酶体）系统，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）的易于释放的钙。从这个酸性细胞器库中释放钙有助于神经元中对基本生理过程至关重要的钙依赖性过程，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。在病理上，在各种神经退行性疾病中都观察到内溶酶体结构和/或功能的紊乱，包括阿尔茨海默病（AD）和 HIV-1 相关的神经认知障碍（HAND）。而且，细胞内钙的失调与这些神经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转导、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，就有可能为新的治疗方法开辟前进的道路。
