ArticleProceedings of the National Academy of Sciences of the United States of America2021
Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- JAK4D, a first-in-class thyrotropin-releasing hormone analogue, reverses scopolamine-induced memory deficits.Brain communications · 2026Article
- Optical, contact-free assessment of brain tissue stiffness and neurodegeneration.Biomedical optics express · 2025Article
- A golden age of muscarinic acetylcholine receptor modulation in neurological diseases.Nature reviews. Drug discovery · 2024Review
- DOTAD: A Database of Therapeutic Antibody Developability.Interdisciplinary sciences, computational life sciences · 2024Article
- New Light on Prions: Putative Role of PrPInternational journal of molecular sciences · 2024Review
- Cholinergic signaling via muscarinic M1 receptor confers resistance to docetaxel in prostate cancer.Cell reports. Medicine · 2024Article
- Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders.Annual review of pharmacology and toxicology · 2024Review
- Review
- Article
- G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.Signal transduction and targeted therapy · 2023Review
- 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
- 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
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
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. Here, we use these same genetic models in concert with murine prion disease, a terminal neurodegenerative disease showing key hallmarks of AD, to establish that phosphorylation/arrestin-dependent signaling delivers neuroprotection that both extends normal animal behavior and prolongs the life span of prion-diseased mice. Our data point to an important neuroprotective property inherent to the M1-receptor and indicate that next generation M1-receptor ligands designed to drive receptor phosphorylation/arrestin-dependent signaling would potentially show low adverse responses while delivering neuroprotection that will slow disease progression.
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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.