ArticleThe Journal of biological chemistry2009
GRK5 deficiency leads to reduced hippocampal acetylcholine level via impaired presynaptic M2/M4 autoreceptor desensitization.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Understanding How Physical Exercise Improves Alzheimer's Disease: Cholinergic and Monoaminergic Systems.Frontiers in aging neuroscience · 2022Review
- GRK5 Deficiency Causes Mild Cognitive Impairment due to Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Review
- Neuropharmacology of Cevimeline and Muscarinic Drugs-Focus on Cognition and Neurodegeneration.International journal of molecular sciences · 2021Review
- The GRKs Reactome: Role in Cell Biology and Pathology.International journal of molecular sciences · 2021Review
- Targeting GRK5 for Treating Chronic Degenerative Diseases.International journal of molecular sciences · 2021Review
- Review
- Dangerous Liaisons: Tau Interaction with Muscarinic Receptors.Current Alzheimer research · 2020Review
- Neurotropin reduces memory impairment and neuroinflammation via BDNF/NF-κB in a transgenic mouse model of Alzheimer's disease.American journal of translational research · 2019Article
- GRK5 - A Functional Bridge Between Cardiovascular and Neurodegenerative Disorders.Frontiers in pharmacology · 2018Review
- The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk.Oncotarget · 2017Article
- Proinflammatory Cytokines Mediate GPCR Dysfunction.Journal of cardiovascular pharmacology · 2017Review
- Neurotropin® alleviates hippocampal neuron damage through a HIF-1α/MAPK pathway.CNS neuroscience & therapeutics · 2017Article
- G Protein-Coupled Receptor Kinases in the Inflammatory Response and Signaling.Advances in immunology · 2017Review
- Magnesium Elevation Promotes Neuronal Differentiation While Suppressing Glial Differentiation of Primary Cultured Adult Mouse Neural Progenitor Cells through ERK/CREB Activation.Frontiers in neuroscience · 2017Article
- GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability.Scientific reports · 2016Article
- G-protein-coupled receptor kinases in inflammation and disease.Genes and immunity · 2015Review
- Disruption of dopamine D1 receptor phosphorylation at serine 421 attenuates cocaine-induced behaviors in mice.Neuroscience bulletin · 2014Article
- Differentiation renders susceptibility to excitotoxicity in HT22 neurons.Neural regeneration research · 2013Article
- Edaravone protects HT22 neurons from H2O2-induced apoptosis by inhibiting the MAPK signaling pathway.CNS neuroscience & therapeutics · 2013Article
- Preparation, drug releasing property and pharmacodynamics of soy isoflavone-loaded chitosan microspheres.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein-coupled receptor kinase 5 (GRK5) deficiency has been linked recently to early Alzheimer disease (AD), but the mechanism by which GRK5 deficiency may contribute to AD pathogenesis remains elusive. Here we report that overexpression of dominant negative mutant of GRK5 (dnGRK5) in a cholinergic neuronal cell line led to decreased acetylcholine (ACh) release. This reduction was fully corrected by pertussis toxin, atropine (a nonselective muscarinic antagonist), or methoctramine (a selective M2/M4 muscarinic receptor antagonist). Consistent with results in cultured cells, high potassium-evoked ACh release in hippocampal slices from young GRK5 knock-out mice was significantly reduced compared with wild type littermates, and this reduced ACh release was also fully corrected by methoctramine. In addition, following treatment with the nonselective muscarinic agonist oxotremorine-M, M2, and M4 receptors underwent significantly reduced internalization in GRK5KO slices compared with wild type slices, as assessed by plasma membrane retention of receptor immunoreactivity, whereas M1 receptor internalization was not affected by loss of GRK5 expression. Moreover, Western blotting revealed no synaptic or cholinergic degenerative changes in young GRK5 knock-out mice. Altogether, these results suggest that GRK5 deficiency leads to a reduced hippocampal ACh release and cholinergic hypofunction by selective impairment of desensitization of presynaptic M2/M4 autoreceptors. Because this nonstructural cholinergic hypofunction precedes the hippocampal cholinergic hypofunction associated with structural cholinergic degeneration and cognitive decline in aged GRK5 knock-out mice, this nonstructural alteration may be an early event contributing to cholinergic degeneration in 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.