Blocking glutamate mGlu₅ receptors with the negative allosteric modulator CTEP improves disease course in SOD1^G93A mouse model of amyotrophic lateral sclerosis.

ABSTRACT:

Background and purpose

The pathogenesis of amyotrophic lateral sclerosis (ALS) is not fully clarified, although excessive glutamate (Glu) transmission and the downstream cytotoxic cascades are major mechanisms for motor neuron death. Two metabotropic glutamate receptors (mGlu₁ and mGlu₅ ) are overexpressed in ALS and regulate cellular disease processes. Expression and function of mGlu₅ receptors are altered at early symptomatic stages in the SOD1^G93A mouse model of ALS and knockdown of mGlu5 receptors in SOD1^G93A mice improved disease progression.

Experimental approach

We treated male and female SOD1^G93A mice with 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP)

SUBMITTER: Milanese M 

PROVIDER: S-EPMC8457068 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature