Readily Releasable Stores of Calcium in Neuronal Endolysosomes: Physiological and Pathophysiological Relevance.

Abstract:

: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.

journal_name

Adv Exp Med Biol

authors

Lakpa KL,Halcrow PW,Chen X,Geiger JD

doi

10.1007/978-3-030-12457-1_27

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

681-697

eissn

0065-2598

issn

2214-8019

journal_volume

1131

pub_type

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