ArticleProceedings of the National Academy of Sciences of the United States of America2019
Intrinsic mutant HTT-mediated defects in oligodendroglia cause myelination deficits and behavioral abnormalities in Huntington disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed.
- Article
- Mutant Huntingtin disrupts neurogenic and astroglial programs via the EZH2-Let-7g-LIN28 axis with rescue by epigenetic modulators.Cell death and differentiation · 2026Article
- DNA methylation profiling in Huntington's disease reveals disease associated changes in the striatum.Clinical epigenetics · 2026Article
- Aberrant medial ganglionic eminence (MGE) GABAergic neurogenesis contributes to Huntington's disease pathogenesis.Neurobiology of disease · 2026Article
- Astrocyte heterogeneity and gliosis in Huntington's disease: Histopathological insights into striatal and white matter pathology.Histology and histopathology · 2026Review
- Differences in white matter detected by ex vivo 9.4 T MRI are associated with axonal changes in the R6/1 model of Huntington's disease.Neurobiology of disease · 2026Article
- Molecular and imaging biomarker responses to brain mutant HTT lowering in a mouse model of Huntington disease.Molecular therapy. Nucleic acids · 2025Article
- The mCells · 2025Review
- BA9 Transcriptomics in Huntington's Disease 80-Gene Signature and MIR219A2-Linked Targets.International journal of molecular sciences · 2025Article
- Gene Therapy of Adrenomyeloneuropathy: Challenges, Target Cells, and Prospectives.Biomedicines · 2025Review
- The role of oligodendroglial dysfunction in Huntington's disease.Journal of Huntington's disease · 2025Review
- The patient-specific mouse model with Foxg1 frameshift mutation provides insights into the pathophysiology of FOXG1 syndrome.Nature communications · 2025Article
- Review
- Progress in AAV-Mediated In Vivo Gene Therapy and Its Applications in Central Nervous System Diseases.International journal of molecular sciences · 2025Review
- Article
- The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation.Neurology international · 2025Review
- Oligodendroglia in Ageing and Age-Dependent Neurodegenerative Diseases.Advances in neurobiology · 2025Review
- Review
- Neuroinflammatory Proteins in Huntington's Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Mapping the glial transcriptome in Huntington's disease using snRNAseq: selective disruption of glial signatures across brain regions.Acta neuropathologica communications · 2024Article
13 more citing papers are in PubMed but not listed here.
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17 authors.
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Abstract
White matter abnormalities are a nearly universal pathological feature of neurodegenerative disorders including Huntington disease (HD). A long-held assumption is that this white matter pathology is simply a secondary outcome of the progressive neuronal loss that manifests with advancing disease. Using a mouse model of HD, here we show that white matter and myelination abnormalities are an early disease feature appearing before the manifestation of any behavioral abnormalities or neuronal loss. We further show that selective inactivation of mutant huntingtin (mHTT) in the NG2+ oligodendrocyte progenitor cell population prevented myelin abnormalities and certain behavioral deficits in HD mice. Strikingly, the improvements in behavioral outcomes were seen despite the continued expression of mHTT in nonoligodendroglial cells including neurons, astrocytes, and microglia. Using RNA-seq and ChIP-seq analyses, we implicate a pathogenic mechanism that involves enhancement of polycomb repressive complex 2 (PRC2) activity by mHTT in the intrinsic oligodendroglial dysfunction and myelination deficits observed in HD. Our findings challenge the long-held dogma regarding the etiology of white matter pathology in HD and highlight the contribution of epigenetic mechanisms to the observed intrinsic oligodendroglial dysfunction. Our results further suggest that ameliorating white matter pathology and oligodendroglial dysfunction may be beneficial for HD.
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