Reduction of glutamate neurotoxicity: A novel therapeutic approach for Niemann-Pick disease, type C1.

ABSTRACT: Niemann-Pick disease, type C1 is a progressive, lethal, neurodegenerative disorder due to endolysosomal storage of unesterified cholesterol. Cerebellar ataxia, as a result of progressive loss of cerebellar Purkinje neurons, is a major symptom of Nieman-Pick disease, type C1. Comparing single cell RNAseq data from control (Npc1^+/+) and mutant (Npc1^-/-) mice, we observed significantly decreased expression of Slc1a3 in Npc1^-/- astrocytes. Slc1a3 encodes a glutamate transporter (GLAST, EAAT1) which functions to decrease glutamate concentrations in the post synaptic space after neuronal firing. Glutamate is an excitatory neurotransmitter and elevated extracellular levels of glutamate can be neurotoxic. Impaired EAAT1 function underlies type-6 episodic ataxia, a

SUBMITTER: Cougnoux A 

PROVIDER: S-EPMC8767495 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature