ArticleNature chemical biology2020
Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Trial
- Advances in Targeting Central Cholinergic Dysfunction for Neurodegenerative Diseases: From Pharmacotherapy to Neuromodulation.CNS neuroscience & therapeutics · 2026Review
- Novel drug treatments for schizophrenia.Nature reviews. Drug discovery · 2026Review
- The clinical implication of β-arrestins-mediated signaling in memory and cognition.Molecular and cellular biochemistry · 2025Review
- A golden age of muscarinic acetylcholine receptor modulation in neurological diseases.Nature reviews. Drug discovery · 2024Review
- Current Findings and Potential Mechanisms of KarXT (Xanomeline-Trospium) in Schizophrenia Treatment.Clinical drug investigation · 2024Review
- Review
- The Impact of Muscarinic Antagonism on Psychosis-Relevant Behaviors and Striatal [Biomedicines · 2023Article
- Phosphorylation barcodes direct biased chemokine signaling at CXCR3.Cell chemical biology · 2023Article
- Structural Insights into M1 Muscarinic Acetylcholine Receptor Signaling Bias between Gαq and β-Arrestin through BRET Assays and Molecular Docking.International journal of molecular sciences · 2023Article
- Establishment of a CaCC-based Cell Model and Method for High-throughput Screening of M3 Receptor Drugs.Cell biochemistry and biophysics · 2023Article
- MScience signaling · 2022Article
- G protein-biased GPR3 signaling ameliorates amyloid pathology in a preclinical Alzheimer's disease mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- GPCRs in Intracellular Compartments: New Targets for Drug Discovery.Biomolecules · 2022Review
- The MProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Muscarinic receptors: from clinic to bench to clinic.Trends in pharmacological sciences · 2022Article
- Targeting the M1 muscarinic acetylcholine receptor in Alzheimer's disease.Neuronal signaling · 2022Review
- Role of Cholinergic Signaling in Alzheimer's Disease.Molecules (Basel, Switzerland) · 2022Review
- DREADDs in Epilepsy Research: Network-Based Review.Frontiers in molecular neuroscience · 2022Review
- Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer's disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-coupled receptor (GPCR) have failed, largely due to cholinergic adverse responses. Employing novel chemogenetic and phosphorylation-deficient, G protein-biased, mouse models, paired with a toolbox of probe molecules, we establish previously unappreciated pharmacologically targetable M1 mAChR neurological processes, including anxiety-like behaviors and hyper-locomotion. By mapping the upstream signaling pathways regulating these responses, we determine the importance of receptor phosphorylation-dependent signaling in driving clinically relevant outcomes and in controlling adverse effects including 'epileptic-like' seizures. We conclude that M1 mAChR ligands that promote receptor phosphorylation-dependent signaling would protect against cholinergic adverse effects in addition to driving beneficial responses such as learning and memory and anxiolytic behavior relevant for the treatment of AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.