ArticleCell death & disease2013
Imbalance of p75(NTR)/TrkB protein expression in Huntington's disease: implication for neuroprotective therapies.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Molecular interplay between Non-coding RNAs and BDNF in Neurodegenerative Disorders: a systematic review.Molecular biology reports · 2026Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Taming the "death receptor": translating the first-in-class p75Journal of translational medicine · 2026Review
- Pharmacological modulation of p75 neurotrophin receptor in microglial cells improves resilience to rotenone cytotoxicity.Frontiers in pharmacology · 2026Article
- The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders.Molecular neurobiology · 2025Review
- Brain-Derived Neurotrophic Factor (BDNF) in Huntington's Disease: Neurobiology and Therapeutic Potential.Current neuropharmacology · 2025Review
- Peripheral Brain-Derived Neurotrophic Factor (BDNF) and Its Regulatory miRNAs as Biological Correlates of Impulsivity in Young Adults.Metabolites · 2024Article
- Thalamic Foxp2 regulates output connectivity and sensory-motor impairments in a model of Huntington's Disease.Cellular and molecular life sciences : CMLS · 2023Article
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington's Disease.Current neuropharmacology · 2023Review
- Current Diagnostic Methods and Non-Coding RNAs as Possible Biomarkers in Huntington's Disease.Genes · 2022Review
- New Frontiers in Neurodegeneration and Regeneration Associated with Brain-Derived Neurotrophic Factor and the rs6265 Single Nucleotide Polymorphism.International journal of molecular sciences · 2022Review
- Altered m6A RNA methylation contributes to hippocampal memory deficits in Huntington's disease mice.Cellular and molecular life sciences : CMLS · 2022Article
- The Role of Brain-Derived Neurotrophic Factor Signaling in Central Nervous System Disease Pathogenesis.Frontiers in human neuroscience · 2022Review
- Neuronal apoptosis induced by morphine withdrawal is mediated by the p75 neurotrophin receptor.Journal of neurochemistry · 2021Article
- Review
- Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington's Disease: Preclinical Evidence with the p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Up-regulation of the p75 neurotrophin receptor is an essential mechanism for HIV-gp120 mediated synaptic loss in the striatum.Brain, behavior, and immunity · 2020Article
- Synaptic RTP801 contributes to motor-learning dysfunction in Huntington's disease.Cell death & disease · 2020Article
- Feeding and food availability modulate brain-derived neurotrophic factor, an orexigen with metabolic roles in zebrafish.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroprotective therapies based on brain-derived neurotrophic factor (BDNF) administration have been proposed for Huntington's disease (HD) treatment. However, our group has recently reported reduced levels of TrkB in HD mouse models and HD human brain suggesting that besides a decrease on BDNF levels a reduction of TrkB expression could also contribute to diminished neurotrophic support in HD. BDNF can also bind to p75 neurotrophin receptor (p75(NTR)) modulating TrkB signaling. Therefore, in this study we have analyzed the levels of p75(NTR) in several HD models, as well as in HD human brain. Our data demonstrates a p75(NTR)/TrkB imbalance in the striatum of two different HD mouse models, Hdh(Q111/111) homozygous knockin mice and R6/1 mice that was also manifested in the putamen of HD patients. The imbalance between TrkB and p75(NTR) levels in a HD cellular model did not affect BDNF-mediated TrkB activation of prosurvival pathways but induced activation of apoptotic cascades as demonstrated by increased JNK phosphorylation. Moreover, BDNF failed to protect mutant huntingtin striatal cells transfected with p75(NTR) against NMDA-mediated excitotoxicity, which was associated with decreased Akt phosphorylation. Interestingly, lack of Akt activation following BDNF and NMDA treatment correlated with increased PP1 levels. Accordingly, pharmacological inhibition of PP1 by okadaic acid (OA) prevented mutant huntingtin striatal cell death induced by NMDA and BDNF. Altogether, our findings demonstrate that the p75(NTR)/TrkB imbalance induced by mutant huntingtin in striatal cells associated with the aberrant activity of PP1 disturbs BDNF neuroprotection likely contributing to increasing striatal vulnerability in HD. On the basis of this data we hypothesize that normalization of p75(NTR) and/or TrkB expression or their signaling will improve BDNF neuroprotective therapies in HD.
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