ArticleMolecular brain2019
Modulation of mTOR and CREB pathways following mGluR5 blockade contribute to improved Huntington's pathology in zQ175 mice.
Article in Molecular brain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 65 citations in OpenAlex.
- Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.Journal of biomedical science · 2026Article
- Metabotropic Glutamate Receptor-Dependent Synaptic Plasticity in Age-Related Neurodegenerative Disorders.Neural plasticity · 2026Review
- Advances and Therapeutic Potential of Anthraquinone Compounds in Neurodegenerative Diseases: A Comprehensive Review.Drug design, development and therapy · 2026Review
- Silmitasertib, an FDA-designated orphan CK2 inhibitor, ameliorates neuropathology and motor dysfunction in a Huntington's disease mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Silmitasertib, an FDA-designated orphan CK2 Inhibitor, ameliorates neuropathology and motor dysfunction in a Huntington's disease mouse model.bioRxiv : the preprint server for biology · 2025Article
- Application of Neurotrophic Factors as a Therapeutic Approach for Neurodegenerative Diseases.Experimental neurobiology · 2025Review
- Inhibition of metabotropic glutamate receptor-5 alleviates hepatic steatosis by enhancing autophagyWorld journal of gastroenterology · 2025Article
- Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.ACS pharmacology & translational science · 2024Review
- Enhanced mGluRCell death & disease · 2024Article
- In vitro modulation of mTOR and mGlur5 influence α-synuclein accumulation.Molecular brain · 2024Article
- Beneficial effects of miR-132/212 deficiency in the zQ175 mouse model of Huntington's disease.Frontiers in neuroscience · 2024Article
- Cytokine enrichment in deep cerebellar nuclei is contributed by multiple glial populations and linked to reduced amyloid plaque pathology.Journal of neuroinflammation · 2023Article
- ASIC1a affects hypothalamic signaling and regulates the daily rhythm of body temperature in mice.Communications biology · 2023Article
- VGLUT3 Deletion Rescues Motor Deficits and Neuronal Loss in the zQ175 Mouse Model of Huntington's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The Role of Neuroglial Metabotropic Glutamate Receptors in Alzheimer's Disease.Current neuropharmacology · 2023Review
- mGluR5 ablation leads to age-related synaptic plasticity impairments and does not improve Huntington's disease phenotype.Scientific reports · 2022Article
- Dioscin-Mediated Autophagy Alleviates MPPMolecules (Basel, Switzerland) · 2022Article
- Group I mGluRs in Therapy and Diagnosis of Parkinson's Disease: Focus on mGluR5 Subtype.Biomedicines · 2022Review
- Review
- 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
Corrections and comments
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Authors and funding
2 authors at 1 institution in 3 countries.
Funding
Abstract
Huntington's disease (HD) is a neurodegenerative disorder caused by a genetic abnormality in the huntingtin gene that leads to a polyglutamine repeat expansion of the huntingtin protein. The cleaved polyglutamine expansion of mutant huntingtin (mHTT) protein can form aggregates strongly correlated with HD progression. We have previously shown that the inhibition of mGluR5 using CTEP, a selective negative allosteric mGluR5 modulator, can delay disease progression and reduce in mHTT aggregates in the zQ175 mouse model of HD. This was paralleled by enhanced catalytic activity of Unc-51-like kinase 1 (ULK1), a kinase modulated by mammalian target of rapamycin (mTOR) and key regulator of autophagy initiation. In the present study, we show that CTEP can correct aberrant phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling detected in zQ175 mice that may underlie the enhanced ULK1 activity and activation of autophagy. We also show that CTEP can facilitate cAMP response element-binding protein (CREB)-mediated expression of brain-derived neurotrophic factor (BDNF) to foster neuronal survival and reduce apoptosis. Taken together, our findings provide the molecular evidence for how targeting mGluR5 using a well-tolerated selective NAM can mitigate two critical mechanisms of neurodegeneration, autophagy and apoptosis.
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