A New Perspective of Lysosomal Cation Channel-Dependent Homeostasis in Alzheimer's Disease

Abstract

Studies have reported typically biophysical lysosomal cation channels including TPCs. Their plausible biological roles are being elucidated by pharmacological, genetic and conventional patch clamp procedures. The best characterized so far among these channels is the ML1 isoform of TRP. The reported TRPs and TPCs are bypass for cation fluxes and are strategic for homeostasis of ionic milieu of the acidic organelles they confine to. Ca(2+) homeostasis and adequate acidic pHL are critically influential for the regulation of a plethora of biological functions these intracellular cation channels perform. In lysosomal ion channel biology, we review: ML1 and TPC2 in Ca(2+) signaling, ML1 and TPC2 in pH(L) regulation. Using Aβ42 and tau proteins found along clathrin endolysosomal internalization pathway (Fig. 3), we proffer a mechanism of abnormal pH(L) and ML1/TPC2-dependent cation homeostasis in AD.

Keywords: AD; Cation homeostasis; Lysosomal Cation Channels; PHL.