ArticleACS pharmacology & translational science2020
mGluR5 Contribution to Neuropathology in Alzheimer Mice Is Disease Stage-Dependent.
Article in ACS pharmacology & translational science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Calcium dysregulation in neurovascular function in Alzheimer's disease: mechanisms, therapeutic targets.GeroScience · 2026Review
- A Framework for Advancing Mechanistic Neurobehavioral Biomarkers in Psychiatry.Biological psychiatry · 2026Review
- Unveiling the Interplay: Neurovascular Coupling, Astrocytes and G Protein-Coupled Receptors in Alzheimer's Disease.ACS pharmacology & translational science · 2025Review
- Insights into the Metabolism, Disposition, and Quantitative Profile of mGlu5 NAM AE90015 with Metabolite Identification and a Novel Integration Method.Molecules (Basel, Switzerland) · 2024Article
- In vitro modulation of mTOR and mGlur5 influence α-synuclein accumulation.Molecular brain · 2024Article
- Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [Alzheimer's research & therapy · 2024Article
- Glutamate Receptor Dysregulation and Platelet Glutamate Dynamics in Alzheimer's and Parkinson's Diseases: Insights into Current Medications.Biomolecules · 2023Review
- Clavulanic Acid Improves Memory Dysfunction and Anxiety Behaviors through Upregulating Glutamatergic Transporters in the Nucleus Accumbens of Mice Repeatedly Exposed to Khat Extract.International journal of molecular sciences · 2023Article
- Comparison of Huntington's disease phenotype progression in male and female heterozygous FDNQ175 mice.Molecular brain · 2023Article
- Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer's disease: Mechanistic insights and potential therapies.Frontiers in neural circuits · 2023Review
- The Role of Neuroglial Metabotropic Glutamate Receptors in Alzheimer's Disease.Current neuropharmacology · 2023Review
- Role of mGlu5 in Persistent Forms of Hippocampal Synaptic Plasticity and the Encoding of Spatial Experience.Cells · 2022Review
- The MK2 cascade mediates transient alteration in mGluR-LTD and spatial learning in a murine model of Alzheimer's disease.Aging cell · 2022Article
- Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q.Science translational medicine · 2022Article
- Group I mGluRs in Therapy and Diagnosis of Parkinson's Disease: Focus on mGluR5 Subtype.Biomedicines · 2022Review
- Metabotropic Glutamate Receptor 5 Antagonism Reduces Pathology and Differentially Improves Symptoms in Male and Female Heterozygous zQ175 Huntington's Mice.Frontiers in molecular neuroscience · 2022Article
- Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?Frontiers in pharmacology · 2022Review
- Blocking glutamate mGluBritish journal of pharmacology · 2021Article
- Effects of blocking mGluR5 on primate dorsolateral prefrontal cortical neuronal firing and working memory performance.Psychopharmacology · 2021Article
- Multi-spectroscopic monitoring of molecular interactions between an amino acid-functionalized ionic liquid and potential anti-Alzheimer's drugs.RSC advances · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and is characterized by a progressive cognitive decline in affected individuals. Current therapeutic strategies are limited in their efficacy and some have proven to be even less effective at later disease stages or after extended use. We previously demonstrated that chronic inhibition of mGluR5 signaling using the selective negative allosteric modulator (NAM) CTEP in APPswe/PS1ΔE9 mice can rescue cognitive function, activating the ZBTB16-mediated autophagy pathway to reduce Aβ, the principal neurotoxic species in AD brains. Here, we evaluated the efficacy of long-term treatment with CTEP in 6 month old APPswe/PS1ΔE9 mice for either 24 or 36 weeks. CTEP maintained its efficacy in reversing working and spatial memory deficits and mitigating neurogliosis in APPswe/PS1ΔE9 mice when administered for 24 weeks. This was paralleled by a significant reduction in Aβ oligomer and plaque load as a result of autophagy activation via ZBTB16 and mTOR-dependent pathways. However, further extension of CTEP treatment for 36 weeks was found ineffective in reversing memory deficit, neurogliosis, or Aβ-related pathology. We found that this loss in CTEP efficacy in 15 month old APPswe/PS1ΔE9 mice was due to the abolished contribution of ZBTB16 and mTOR-mediated signaling to AD neuropathology at this advanced disease stage. Our findings indicate that the contribution of pathological mGluR5-signaling to AD may shift as the disease progresses. Thus, we provide the first evidence that the underlying pathophysiological mechanism(s) of AD may unfold along the course of the disease and treatment strategies should be modified accordingly to ensure maximal therapeutic outcomes.
Identifiers
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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.