ArticleThe Journal of clinical investigation2017
M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
46 citing papers in PubMed, 79 citations in OpenAlex.
- Trial
- Advances in Targeting Central Cholinergic Dysfunction for Neurodegenerative Diseases: From Pharmacotherapy to Neuromodulation.CNS neuroscience & therapeutics · 2026Review
- Article
- Optical, contact-free assessment of brain tissue stiffness and neurodegeneration.Biomedical optics express · 2025Article
- Limbic system synaptic dysfunctions associated with prion disease onset.Acta neuropathologica communications · 2024Article
- Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling.Cell communication and signaling : CCS · 2024Article
- Article
- A golden age of muscarinic acetylcholine receptor modulation in neurological diseases.Nature reviews. Drug discovery · 2024Review
- Prion diseases disrupt glutamate/glutamine metabolism in skeletal muscle.PLoS pathogens · 2024Article
- The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses.Current opinion in neurobiology · 2024Review
- A comprehensive assessment of the cholinergic-supporting and cognitive-enhancing effects of Rosa damascena Mill. (Damask rose) essential oil on scopolamine-induced amnestic rats.Brain and behavior · 2024Article
- Analysing the effect caused by increasing the molecular volume in M1-AChR receptor agonists and antagonists: a structural and computational study.RSC advances · 2024Article
- New Light on Prions: Putative Role of PrPInternational journal of molecular sciences · 2024Review
- Computational prognostic evaluation of Alzheimer's drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches.Scientific reports · 2023Article
- Novel Combination of Choline withInternational journal of molecular sciences · 2023Article
- The Evaluation of Rac1 Signaling as a Potential Therapeutic Target of Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Cross-diagnostic determinants of cognitive functioning: the muscarinic cholinergic receptor as a model system.Translational psychiatry · 2023Review
- Small molecule allosteric modulation of the adenosine AFrontiers in endocrinology · 2023Review
- MScience signaling · 2022Article
- The MProceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
The current frontline symptomatic treatment for Alzheimer's disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholinesterase. This approach leads to profound dose-related adverse effects. An alternative strategy is to selectively target muscarinic acetylcholine receptors, particularly the M1 muscarinic acetylcholine receptor (M1 mAChR), which was previously shown to have procognitive activity. However, developing M1 mAChR-selective orthosteric ligands has proven challenging. Here, we have shown that mouse prion disease shows many of the hallmarks of human AD, including progressive terminal neurodegeneration and memory deficits due to a disruption of hippocampal cholinergic innervation. The fact that we also show that muscarinic signaling is maintained in both AD and mouse prion disease points to the latter as an excellent model for testing the efficacy of muscarinic pharmacological entities. The memory deficits we observed in mouse prion disease were completely restored by treatment with benzyl quinolone carboxylic acid (BQCA) and benzoquinazoline-12 (BQZ-12), two highly selective positive allosteric modulators (PAMs) of M1 mAChRs. Furthermore, prolonged exposure to BQCA markedly extended the lifespan of diseased mice. Thus, enhancing hippocampal muscarinic signaling using M1 mAChR PAMs restored memory loss and slowed the progression of mouse prion disease, indicating that this ligand type may have clinical benefit in diseases showing defective cholinergic transmission, such as AD.
Indexed as
Identifiers
What OpenQuestion holds
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.