ArticleHuman molecular genetics2011
Mitogen- and stress-activated protein kinase 1-induced neuroprotection in Huntington's disease: role on chromatin remodeling at the PGC-1-alpha promoter.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- MSK1 mediates BDNF-dependent MeCP2-S421 phosphorylation in postnatal striatal development and psychiatric-relevant behaviours.Molecular psychiatry · 2026Article
- Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.Molecular neurodegeneration · 2026Article
- Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in lentiviral vectors for gene therapy.Science China. Life sciences · 2021Review
- Epigenetic Regulation of Neuroinflammation in Parkinson's Disease.International journal of molecular sciences · 2021Review
- PGC-1α, Sirtuins and PARPs in Huntington's Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All.Neurochemical research · 2019Review
- Huntington's Disease and Mitochondria.Neurotoxicity research · 2017Review
- Grifolin inhibits tumor cells adhesion and migration via suppressing interplay between PGC1α and Fra-1 / LSF- MMP2 / CD44 axes.Oncotarget · 2016Article
- Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications.The international journal of neuropsychopharmacology · 2016Article
- Does PGC1α/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders?Neuromolecular medicine · 2016Review
- miR-196a Ameliorates Cytotoxicity and Cellular Phenotype in Transgenic Huntington's Disease Monkey Neural Cells.PloS one · 2016Article
- Emerging Roles of the Mitogen and Stress Activated Kinases MSK1 and MSK2.Frontiers in cell and developmental biology · 2016Review
- Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease.Human molecular genetics · 2015Article
- mRNA expression levels of PGC-1α in a transgenic and a toxin model of Huntington's disease.Cellular and molecular neurobiology · 2015Article
- Invited review: decoding the pathophysiological mechanisms that underlie RNA dysregulation in neurodegenerative disorders: a review of the current state of the art.Neuropathology and applied neurobiology · 2015Review
- Transcription, epigenetics and ameliorative strategies in Huntington's Disease: a genome-wide perspective.Molecular neurobiology · 2015Review
- Possible involvement of self-defense mechanisms in the preferential vulnerability of the striatum in Huntington's disease.Frontiers in cellular neuroscience · 2014Review
- Peroxisome proliferator-activated receptors and Alzheimer's disease: hitting the blood-brain barrier.Molecular neurobiology · 2013Review
- Neuroprotective effects of psychotropic drugs in Huntington's disease.International journal of molecular sciences · 2013Review
- Multiple Aspects of Gene Dysregulation in Huntington's Disease.Frontiers in neurology · 2013Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is a neurodegenerative disorder due to abnormal polyglutamine expansion in huntingtin protein (Exp-Htt). This expansion causes protein aggregation, leading to neuronal dysfunction and death. We have previously shown that mitogen- and stress-activated kinase (MSK-1), a nuclear protein kinase involved in chromatin remodeling through histone H3 phosphorylation, is deficient in the striatum of HD patients and model mice. Restoring MSK-1 expression in cultured striatal cells prevented neuronal dysfunction and death induced by Exp-Htt. Here we extend these observations in a rat model of HD based on striatal lentiviral expression of Exp-Htt (LV-Exp-HTT). MSK-1 overexpression attenuated Exp-Htt-induced down-regulation of DARPP-32 expression 4 and 10 weeks after infection and enhanced NeuN staining after 10 weeks. LV-MSK-1 induced constitutive hyperphosphorylation of H3 and cAMP-responsive element binding protein (CREB), indicating that MSK-1 has spontaneous catalytic activity. MSK-1 overexpression also upregulated peroxisome proliferator-activated receptor γ coactivator alpha (PGC-1α), a transcriptional co-activator involved in mitochondrial biogenesis. Chromatin immunoprecipitation indicated that transcriptional regulation of PGC-1α is directly linked to increased binding of MSK-1, along with H3 and CREB phosphorylation of the PGC-1α promoter. MSK-1 knock-out mice showed spontaneous striatal atrophy as they aged, as well as higher susceptibility to systemic administration of the mitochondrial neurotoxin 3-NP. These results indicate that MSK-1 activation is an important and key event in the signaling cascade that regulates PGC-1α expression. Strategies aimed at restoring MSK-1 expression in the striatum might offer a new therapeutic approach to HD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.