GM1-gangliosidosis model in neurodegeneration

The researchers find that, in GM1- gangliosidosis mice, neuronal accumulation of GM1 at the endoplasmic reticulum-plasma membrane (ER-PM) junctions.

 They show that GM1 binds pNMDAR at the ER-PM junctions, altering intracellular Ca²⁺ concentrations.

This results in pNMDAR-mediated Ca²⁺ signaling and increased BDNF levels activate the ERK leading to increased synaptogenesis.

 This leads to increased synaptic spine density without an increase in synaptic connectivity, contributing to the neurodegeneration characteristic of the disease.

https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00445-5

https://sciencemission.com/Altered-GM1-catabolism-affects-NMDAR-mediated-Ca2-signaling-at-ER-PM-junctions-and-increases-synaptic-spine-formation-in-a-GM1-gangliosidosis-model