ArticleBrain pathology (Zurich, Switzerland)2017
MAP2 Splicing is Altered in Huntington's Disease.
Article in Brain pathology (Zurich, Switzerland), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- The small giant actor in the pathogenesis of neurodegenerative diseases: Microtubules.Metabolic brain disease · 2026Review
- Phosphorylation enables progressive microtubule-associated protein proteolysis and functionalisation during neural development.bioRxiv : the preprint server for biology · 2025Article
- Exploring the potential role of microtubule associated proteins-2 in the pathogenesis of HIV associated neurocognitive disorders.Neurotoxicity research · 2025Review
- Role of Glutamate Receptor-related Biomarkers in the Etiopathogenesis of ADHD.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2024Article
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- Towards understandings of serine/arginine-rich splicing factors.Acta pharmaceutica Sinica. B · 2023Review
- Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease.Nature communications · 2023Article
- Tubulin Cytoskeleton in Neurodegenerative Diseases-not Only Primary Tubulinopathies.Cellular and molecular neurobiology · 2023Review
- Review
- SUPT4H1-edited stem cell therapy rescues neuronal dysfunction in a mouse model for Huntington's disease.NPJ Regenerative medicine · 2022Article
- More than a marker: potential pathogenic functions of MAP2.Frontiers in molecular neuroscience · 2022Article
- Targeting Splicing Factor SRSF6 for Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Pathogenic SREK1 decrease in Huntington's disease lowers TAF1 mimicking X-linked dystonia parkinsonism.Brain : a journal of neurology · 2020Article
- Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease.Brain : a journal of neurology · 2020Article
- P2X7 Receptor Upregulation in Huntington's Disease Brains.Frontiers in molecular neuroscience · 2020Article
- An Antagonistic Axon-Dendrite Interplay Enables Efficient Neuronal Repair in the Adult Zebrafish Central Nervous System.Molecular neurobiology · 2019Article
- Structure and Functions of Microtubule Associated Proteins Tau and MAP2c: Similarities and Differences.Biomolecules · 2019Review
- Altered Levels and Isoforms of Tau and Nuclear Membrane Invaginations in Huntington's Disease.Frontiers in cellular neuroscience · 2019Review
- Tau-positive nuclear indentations in P301S tauopathy mice.Brain pathology (Zurich, Switzerland) · 2017Article
- Reduction of Huntington's Disease RNA Foci by CAG Repeat-Targeting Reagents.Frontiers in cellular neuroscience · 2017Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dendritic alteration of striatal medium spiny neurons is one of the earliest morphological abnormalities in Huntington's disease (HD). The main microtubule-associated protein in dendrites is MAP2. The low-molecular weight isoforms of MAP2 (LMW-MAP2) are the juvenile forms resulting from exclusion of the sequence encoded by exons E7-E9 and are downregulated after the early stages of neuronal development when E7-E9 exon-including high-molecular weight isoforms (HMW-MAP2) are favored. Splicing alteration has recently been proposed to contribute to HD in view of two pathogenic missplicing events resulting in a highly toxic N-terminal version of mutant huntingtin and in a detrimental imbalance in MAP Tau isoforms with three or four tubulin-binding repeats. Both splicing events are postulated targets of the SR splicing factor SRSF6 which has recently been reported to be dramatically altered in HD. SR proteins often regulate functionally related sets of genes and SRSF6 targets are enriched in genes involved in brain organogenesis including several actin-and tubulin-binding proteins. Here we hypothesized that MAP2 might be target of SRSF6 and altered in HD. By SRSF6 knockdown in neuroblastoma cells, we demonstrate that splicing of MAP2 E7-E9 exons is affected by SRSF6. We then show a disbalance in LMW and HMW MAP2 mRNA isoforms in HD striatum in favor of the juvenile LMW forms together with a decrease in total MAP2 mRNA. This is accompanied by a global decrease in total MAP2 protein due to almost total disappearance of HMW-MAP2 isoforms with preservation of LMW-MAP2 isoforms. Accordingly, the predominant dendritic MAP2 staining in striatal neuropil of control subjects is absent in HD cases. In these, MAP2-immunoreactivity is faint and restricted to neuronal cell bodies often showing a sharp boundary at the base of dendrites. Together, our results highlight the importance of splicing alteration in HD and suggest that MAP2 alteration contributes to dendritic atrophy.
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