TRPM8 as a potential target in neurodegenerative diseases

Abstract

AbstractBackgroundCholesterol is required by the neuronal cells for a normal brain functions as it affects membrane fluidity and ion channel functions by disrupting calcium homeostasis and neuronal loss1. Synthesis of cholesterol occurs in glial cells like astrocytes and get transported into neurons and intracellular organelles. Any deregulation in these transport leads to several neurodegenerative diseases2,3. TRPM8 cation channel has been found to contain conserved cholesterol binding motifs in its sequences that indicates its potential role in cholesterol mediated functions4.MethodConservation analysis of cholesterol binding motifs has been performed using CARC and CRAC sequences and docking of cholesterol with TRPM8 Cryo EM structure has been performed in Autodock. For in‐vitro studies, peripheral neurons were grown in cholesterol reduced condition. Co‐localization has been studied between TRPM8 and lipid‐raft marker by immunostaining.ResultTRPM8 has conserved cholesterol binding motifs in its structure. In‐vitro study shows that TRPM8 get localized on cholesterol enriched lipid‐raft on the plasma membrane more when cholesterol is reduced. The recruitment of TRPM8 protein also seems to increase in neuronal cell line after cholesterol reduction.ConclusionTRPM8 might have a cholesterol mediated role in neuronal cell dynamics which can be potential target for neurodegenerative diseases.