ArticleHuman molecular genetics2019
Mutant huntingtin reduction in astrocytes slows disease progression in the BACHD conditional Huntington's disease mouse model.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 141 citations in OpenAlex.
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Mutant huntingtin expression in somatostatin-positive interneurons contributes to neurophysiological and behavioral phenotypes in BACHD mice.Disease models & mechanisms · 2026Article
- Astrocyte heterogeneity and gliosis in Huntington's disease: Histopathological insights into striatal and white matter pathology.Histology and histopathology · 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
- Ngn2 and Isl1-mediated astrocyte-to-neuron conversion in vivo promotes functional recovery after spinal cord injury.Cell reports. Medicine · 2025Article
- 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
- Review
- Astrocyte-neuron combined targeting for CYP46A1 gene therapy in Huntington's disease.Acta neuropathologica communications · 2025Article
- Neuroinflammation in Huntington's disease: Causes, consequences, and treatment strategies.Journal of Huntington's disease · 2025Review
- In Vitro Efficacy of PEI-Derived Lipopolymers in Silencing of Toxic Proteins in a Neuronal Model of Huntington's Disease.Pharmaceutics · 2025Article
- Neuroinflammatory Proteins in Huntington's Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Modulation of SNARE-dependent exocytosis in astrocytes improves neuropathology in Huntington's disease.Disease models & mechanisms · 2024Article
- Mapping the glial transcriptome in Huntington's disease using snRNAseq: selective disruption of glial signatures across brain regions.Acta neuropathologica communications · 2024Article
- Multi-omic analysis of Huntington's disease reveals a compensatory astrocyte state.Nature communications · 2024Article
- Plasma GFAP and its association with disease severity in Huntington's disease.Journal of neurology · 2024Article
- Microglia and complement mediate early corticostriatal synapse loss and cognitive dysfunction in Huntington's disease.Nature medicine · 2023Article
- Astrocytes in human central nervous system diseases: a frontier for new therapies.Signal transduction and targeted therapy · 2023Review
- Multi-OMIC analysis of Huntington disease reveals a neuroprotective astrocyte state.bioRxiv : the preprint server for biology · 2023Article
- An altered extracellular matrix-integrin interface contributes to Huntington's disease-associated CNS dysfunction in glial and vascular cells.Human molecular genetics · 2023Article
- Astrocytic contributions to Huntington's disease pathophysiology.Annals of the New York Academy of Sciences · 2023Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Neuronal and non-neuronal cells express the huntingtin (HTT) protein, yet neurodegeneration in Huntington's disease (HD) is largely selective, affecting most prominently striatal medium spiny neurons and cortical pyramidal neurons. Selective toxicity of full-length human mutant HTT (fl-mHTT) may be due in part to its expression in non-neuronal cells. While studies suggest neuronal-glial interactions are important in HD and fl-mHTT is expressed in astrocytes, it has not been determined whether the expression of fl-mHTT in astrocytes is necessary for HD pathogenesis. To directly assess the necessity of fl-mHTT in astrocytes for HD pathogenesis, we used a mouse genetic approach and bred the conditional mHTT-expressing BACHD mouse model with GFAP-CreERT2 mice. We show that GFAP-CreERT2 expression in these mice is highly selective for astrocytes, and we are able to significantly reduce the expression of fl-mHTT protein in the striatum and cortex of BACHD/GFAP-CreERT2-tam mice. We performed behavioral, electrophysiological and neuropathological analyses of BACHD and BACHD/GFAP-CreERT2-tam mice. Behavioral analyses of BACHD/GFAP-CreERT2-tam mice demonstrate significant improvements in motor and psychiatric-like phenotypes. We observe improvements in neuropathological and electrophysiological phenotypes in BACHD/GFAP-CreERT2-tam mice compared to BACHD mice. We observed a restoration of the normal level αB-crystallin in the striatum of the BACHD/GFAP-CreERT2 mice, indicating a cell autonomous effect of mHTT on its expression. Taken together, this work indicates that astrocytes are important contributors to the progression of the behavioral and neuropathological phenotypes observed in HD.
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