ArticleThe Journal of biological chemistry2010
Impaired TrkB-mediated ERK1/2 activation in huntington disease knock-in striatal cells involves reduced p52/p46 Shc expression.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- Roles of MAPKs, Including Those Activated by BDNF/TrkB, and Their Contribution in Neurodegenerative Diseases.International journal of molecular sciences · 2026Review
- Fingolimod Effects on Motor Function and BDNF-TrkB Signaling in a Huntington's Mouse Model Are Disease-Stage-Dependent.International journal of molecular sciences · 2026Article
- The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders.Molecular neurobiology · 2025Review
- AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.Translational neurodegeneration · 2025Review
- Motor skill learning modulates striatal extracellular vesicles' content in a mouse model of Huntington's disease.Cell communication and signaling : CCS · 2024Article
- A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice.Disease models & mechanisms · 2024Article
- Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2.EMBO molecular medicine · 2023Article
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- HTT (huntingtin) and RAB7 co-migrate retrogradely on a signaling LAMP1-containing late endosome during axonal injury.Autophagy · 2023Article
- Failure to Thrive: Impaired BDNF Transport along the Cortical-Striatal Axis in Mouse Q140 Neurons of Huntington's Disease.Biology · 2023Article
- Molecular Pathophysiological Mechanisms in Huntington's Disease.Biomedicines · 2022Review
- Functional characterization and potential therapeutic avenues for variants in the NTRK2 gene causing developmental and epileptic encephalopathies.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2022Article
- Inhibition of p38 Mitogen-Activated Protein Kinase Ameliorates HAP40 Depletion-Induced Toxicity and Proteasomal Defect in Huntington's Disease Model.Molecular neurobiology · 2021Article
- Functional analysis of brain derived neurotrophic factor (BDNF) in Huntington's disease.Aging · 2021Article
- Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Protects Striatal Cells and Improves Motor Function in Huntington's Disease Models: Role of PAC1 Receptor.Frontiers in pharmacology · 2021Article
- Modulation of dopamine DeLife · 2020Article
- Twist1 Plays an Anti-apoptotic Role in Mutant Huntingtin Expression Striatal Progenitor Cells.Molecular neurobiology · 2020Article
- Cell-Autonomous and Non-cell-Autonomous Pathogenic Mechanisms in Huntington's Disease: Insights from In Vitro and In Vivo Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Article
- Early Downregulation of p75Molecular neurobiology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Altered neurotrophic support as a result of reduced brain-derived neurotrophic factor (BDNF) expression and trafficking has been revealed as a key factor in Huntington disease (HD) pathology. BDNF binds to and activates the tyrosine kinase receptor TrkB, leading to activation of intracellular signaling pathways to promote differentiation and cell survival. In order to design new neuroprotective therapies based on BDNF delivery, it is important to define whether BDNF-mediated TrkB signaling is affected in HD. Here, we demonstrate reduced TrkB-mediated Ras/MAPK/ERK1/2 signaling but unchanged phosphatidylinositol 3-kinase/Akt and phospholipase Cgamma activation in knock-in HD striatal cells. Altered BDNF-mediated ERK1/2 activation in mutant huntingtin cells is associated with reduced expression of p52/p46 Shc docking proteins. Notably, reduced BDNF-induced ERK1/2 activation increases the sensitivity of mutant huntingtin striatal cells to oxidative damage. Accordingly, pharmacological activation of the MAPK pathway with PMA prevents cell death induced by oxidative stress. Taken together, our results suggest that in addition to reduced BDNF, diminished Ras/MAPK/ERK1/2 activation is involved in neurotrophic deficits associated with HD pathology. Therefore, pharmacological approaches aimed to directly modulate the MAPK/ERK1/2 pathway may represent a valuable therapeutic strategy in HD.
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