New Positive TRPC6 Modulator Penetrates Blood-Brain Barrier, Eliminates Synaptic Deficiency and Restores Memory Deficit in 5xFAD Mice.

ABSTRACT: Synapse loss in the brain of Alzheimer's disease patients correlates with cognitive dysfunctions. Drugs that limit synaptic loss are promising pharmacological agents. The transient receptor potential cation channel, subfamily C, member 6 (TRPC6) regulates the formation of an excitatory synapse. Positive regulation of TRPC6 results in increased synapse formation and enhances learning and memory in animal models. The novel selective TRPC6 agonist, 3-(3-,4-Dihydro-6,7-dimethoxy-3,3-dimethyl-1-isoquinolinyl)-2H-1-benzopyran-2-one, has recently been identified. Here we present in silico, in vitro, ex vivo, pharmacokinetic and in vivo studies of this compound. We demonstrate that it binds to the extracellular agonist binding site of the human TRPC6, protects hippocampal mushroom spines from amyl

SUBMITTER: Zernov N 

PROVIDER: S-EPMC9653995 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature