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Lysosomes are key acidic Ca 2+ stores. The principle Ca 2+ -permeable channels of the lysosome are TRP mucolipins (TRPMLs) and NAADP-regulated two-pore channels (TPCs). Recent studies, reviewed in this collection, have linked numerous neurodegenerative diseases to both gain and loss of function of TRPMLs/TPCs, as well as to defects in acidic Ca 2+ store content. These diseases span rare lysosomal storage disorders such as Mucolipidosis Type IV and Niemann-Pick disease, type C, through to more common ones such as Alzheimer and Parkinson disease. Cellular phenotypes, underpinned by endo-lysosomal trafficking defects, are reversed by chemical or molecular targeting of TRPMLs and TPCs. Lysosomal Ca 2+ channels therefore emerge as potential druggable targets in combatting neurodegeneration.

Deviant Lysosomal Ca2+ Signalling in Neurodegeneration. An Introduction

Deviant Lysosomal Ca²⁺ Signalling in Neurodegeneration. An Introduction