ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Expanded-polyglutamine huntingtin protein suppresses the secretion and production of a chemokine (CCL5/RANTES) by astrocytes.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 108 citations in OpenAlex.
- Neuroinflammatory Proteins in Huntington's Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications.International journal of molecular sciences · 2024Review
- CCL5 is essential for axonogenesis and neuronal restoration after brain injury.Journal of biomedical science · 2024Article
- Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing.International journal of molecular sciences · 2023Review
- Severity- and Time-Dependent Activation of Microglia in Spinal Cord Injury.International journal of molecular sciences · 2023Article
- The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington's Disease.Current neuropharmacology · 2023Review
- Pathogenesis of Huntington's Disease: An Emphasis on Molecular Pathways and Prevention by Natural Remedies.Brain sciences · 2022Review
- Neuroinflammation in Huntington's Disease: A Starring Role for Astrocyte and Microglia.Current neuropharmacology · 2022Review
- CCL5 promotion of bioenergy metabolism is crucial for hippocampal synapse complex and memory formation.Molecular psychiatry · 2021Article
- Astrocytes: a double-edged sword in neurodegenerative diseases.Neural regeneration research · 2021Review
- Vav3-Deficient Astrocytes Enhance the Dendritic Development of Hippocampal Neurons in an Indirect Co-culture System.Frontiers in cellular neuroscience · 2021Article
- Ferroptosis Mediated by Lipid Reactive Oxygen Species: A Possible Causal Link of Neuroinflammation to Neurological Disorders.Oxidative medicine and cellular longevity · 2021Review
- Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis.Frontiers in neurology · 2020Review
- Chromatin accessibility and transcription dynamics during in vitro astrocyte differentiation of Huntington's Disease Monkey pluripotent stem cells.Epigenetics & chromatin · 2019Article
- Galectin-3 is required for the microglia-mediated brain inflammation in a model of Huntington's disease.Nature communications · 2019Article
- Reactive Astrocytes in Neurodegenerative Diseases.Aging and disease · 2019Review
- Mutant huntingtin reduction in astrocytes slows disease progression in the BACHD conditional Huntington's disease mouse model.Human molecular genetics · 2019Article
- Mortal engines: Mitochondrial bioenergetics and dysfunction in neurodegenerative diseases.Pharmacological research · 2018Review
- Pomalidomide Ameliorates H₂O₂-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects.International journal of molecular sciences · 2018Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is a hereditary neurological disease caused by expended CAG repeats in the HD gene, which codes for a protein called Huntingtin (Htt). The resultant mutant Huntingtin (mHtt) forms aggregates in neurons and causes neuronal dysfunction. In astrocytes, the largest population of brain cells, mHtt also exists. We report herein that astrocyte-conditioned medium (ACM) collected from astrocytes of R6/2 mice (a mouse model of HD) caused primary cortical neurons to grow less-mature neurites, migrate more slowly, and exhibit lower calcium influx after depolarization than those maintained in wild-type (WT) ACM. Using a cytokine antibody array and ELISA assays, we demonstrated that the amount of a chemokine [chemokine (C-C motif) ligand 5 (CCL5)/regulated on activation normal T cell expressed and secreted (RANTES)] released by R6/2 astrocytes was much less than that by WT astrocytes. When cortical neurons were treated with the indicated ACM, supplementation with recombinant CCL5/RANTES ameliorated the neuronal deficiency caused by HD-ACM, whereas removing CCL5/RANTES from WT-ACM using an anti-CCL5/RANTES antibody mimicked the effects evoked by HD-ACM. Quantitative PCR and promoter analyses demonstrated that mHtt hindered the activation of the CCL5/RANTES promoter by reducing the availability of nuclear factor kappaB-p65 and, hence, reduced the transcript level of CCL5/RANTES. Moreover, ELISA assays and immunocytochemical staining revealed that mHtt retained the residual CCL5/RANTES inside R6/2 astrocytes. In line with the above findings, elevated cytosolic CCL5/RANTES levels were also observed in the brains of two mouse models of HD [R6/2 and Hdh((CAG)150)] and human HD patients. These findings suggest that mHtt hinders one major trophic function of astrocytes which might contribute to the neuronal dysfunction of HD.
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