Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease.

ABSTRACT: There are currently no treatments that can slow the progression of neurodegenerative diseases, such as Alzheimer's disease (AD). There is, however, a growing body of evidence that activation of the M1 muscarinic acetylcholine receptor (M1-receptor) can not only restore memory loss in AD patients but in preclinical animal models can also slow neurodegenerative disease progression. The generation of an effective medicine targeting the M1-receptor has however been severely hampered by associated cholinergic adverse responses. By using genetically engineered mouse models that express a G protein-biased M1-receptor, we recently established that M1-receptor mediated adverse responses can be minimized by ensuring activating ligands maintain receptor phosphorylation/arrestin-dependent signaling. H

SUBMITTER: Scarpa M 

PROVIDER: S-EPMC8685681 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature