ArticleHuman molecular genetics2013
Small-molecule TrkB receptor agonists improve motor function and extend survival in a mouse model of Huntington's disease.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 127 citations in OpenAlex.
- Natural products proposed for the management of Huntington's disease (HD): a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders.Molecular neurobiology · 2025Review
- Emerging Ferroptosis Involvement in Amyotrophic Lateral Sclerosis Pathogenesis: Neuroprotective Activity of Polyphenols.Molecules (Basel, Switzerland) · 2025Review
- The Role of Brain-Derived Neurotrophic Factor as an Essential Mediator in Neuronal Functions and the Therapeutic Potential of Its Mimetics for Neuroprotection in Neurologic and Psychiatric Disorders.Molecules (Basel, Switzerland) · 2025Review
- Brain-Derived Neurotrophic Factor (BDNF) in Huntington's Disease: Neurobiology and Therapeutic Potential.Current neuropharmacology · 2025Review
- BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy.Journal of cellular and molecular medicine · 2024Review
- Brain-Periphery Interactions in Huntington's Disease: Mediators and Lifestyle Interventions.International journal of molecular sciences · 2024Review
- Activation of TrkB signaling mitigates cerebellar anomalies caused by Rbm4-Bdnf deficiency.Communications biology · 2023Article
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- 7,8-dihydroxyflavone enhances long-term spatial memory and alters brain volume in wildtype mice.Frontiers in systems neuroscience · 2023Article
- The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington's Disease.Current neuropharmacology · 2023Review
- Temporal Characterization of Behavioral and Hippocampal Dysfunction in the YAC128 Mouse Model of Huntington's Disease.Biomedicines · 2022Article
- TrkB Receptor Agonist 7,8 Dihydroxyflavone is Protective Against the Inner Retinal Deficits Induced by Experimental Glaucoma.Neuroscience · 2022Article
- Metabolic protection by the dietary flavonoid 7,8-dihydroxyflavone requires an intact gut microbiome.Frontiers in nutrition · 2022Article
- Huntington's disease phenotypes are improved via mTORC1 modulation by small molecule therapy.PloS one · 2022Article
- Temporal Phenotypic Changes in Huntington's Disease Models for Preclinical Studies.Journal of Huntington's disease · 2022Article
- Article
- 7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development.Current neuropharmacology · 2022Review
- Immortalized striatal precursor neurons from Huntington's disease patient-derived iPS cells as a platform for target identification and screening for experimental therapeutics.Human molecular genetics · 2021Article
- Rescuing mitochondria in traumatic brain injury and intracerebral hemorrhages - A potential therapeutic approach.Neurochemistry international · 2021Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Huntington's disease (HD) is a fatal neurodegenerative disease characterized by abnormal motor coordination, cognitive decline and psychiatric disorders. This disease is caused by an expanded CAG trinucleotide repeat in the gene encoding the protein huntingtin. Reduced levels of brain-derived neurotrophic factor (BDNF) in the brain, which results from transcriptional inhibition and axonal transport deficits mediated by mutant huntingtin, have been suggested as critical factors underlying selective neurodegeneration in both HD patients and HD mouse models. BDNF activates its high-affinity receptor TrkB and promotes neuronal survival; restoring BDNF signaling is thus of particular therapeutic interest. In the present study, we evaluated the ability of a small-molecule TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and its synthetic derivative 4'-dimethylamino-7,8- dihydroxyflavone (4'-DMA-7,8-DHF) to protect neurons in the well-characterized N171-82Q HD mouse model. We found that chronic administration of 7, 8-DHF (5 mg/kg) or 4'-DMA-7,8-DHF (1 mg/kg) significantly improved motor deficits, ameliorated brain atrophy and extended survival in these N171-82Q HD mice. Moreover, 4'-DMA-7,8-DHF preserved DARPP32 levels in the striatum and rescued mutant huntingtin-induced impairment of neurogenesis in the N171-82Q HD mice. These data highlight consideration of TrkB as a therapeutic target in HD and suggest that small-molecule TrkB agonists that penetrate the brain have high potential to be further tested in clinical trials of 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.