ArticleHuman molecular genetics2009
Transcriptional dysregulation of TrkA associates with neurodegeneration in spinocerebellar ataxia type 17.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- Molecular Mechanisms of Spinocerebellar Ataxia Type 17.Molecular neurobiology · 2025Review
- The roles of TAF1 in neuroscience and beyond.Royal Society open science · 2024Review
- Functional implications of paralog genes in polyglutamine spinocerebellar ataxias.Human genetics · 2023Review
- Decoding Neurodegeneration: A Comprehensive Review of Molecular Mechanisms, Genetic Influences, and Therapeutic Innovations.International journal of molecular sciences · 2023Review
- Review
- A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases.Frontiers in molecular neuroscience · 2022Review
- Conventional MRI findings in hereditary degenerative ataxias: a pictorial review.Neuroradiology · 2021Review
- Increased hippocampal TrkA expression ameliorates cranial radiation‑induced neurogenesis impairment and cognitive deficit via PI3K/AKT signaling.Oncology reports · 2020Article
- Cerebellum-enriched protein INPP5A contributes to selective neuropathology in mouse model of spinocerebellar ataxias type 17.Nature communications · 2020Article
- Aberrant Cerebellar Circuitry in the Spinocerebellar Ataxias.Frontiers in neuroscience · 2020Review
- Gene Deregulation and Underlying Mechanisms in Spinocerebellar Ataxias With Polyglutamine Expansion.Frontiers in neuroscience · 2020Review
- The selective TrkA agonist, gambogic amide, promotes osteoblastic differentiation and improves fracture healing in mice.Journal of musculoskeletal & neuronal interactions · 2019Article
- Piperine ameliorates SCA17 neuropathology by reducing ER stress.Molecular neurodegeneration · 2018Article
- Modulation of Molecular Chaperones in Huntington's Disease and Other Polyglutamine Disorders.Molecular neurobiology · 2017Review
- Evidence of TAF1 dysfunction in peripheral models of X-linked dystonia-parkinsonism.Cellular and molecular life sciences : CMLS · 2016Article
- Molecular mechanisms underlying Spinocerebellar Ataxia 17 (SCA17) pathogenesis.Rare diseases (Austin, Tex.) · 2016Article
- Precision medicine in spinocerebellar ataxias: treatment based on common mechanisms of disease.Annals of translational medicine · 2016Review
- Molecular Mechanism of Switching of TrkA/p75(NTR) Signaling in Monocrotophos Induced Neurotoxicity.Scientific reports · 2015Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
TATA binding protein (TBP), a universal transcription factor, is broadly required by nuclear RNA polymerases for the initiation of transcription. TBP contains a polymorphic polyglutamine tract in its N-terminal region, and expansion of this tract leads to spinocerebellar ataxia type 17 (SCA17), one of nine dominantly inherited neurodegenerative diseases caused by polyglutamine expansion in the affected proteins. The expanded polyglutamine proteins are ubiquitously expressed, but cause selective and characteristic neurodegeneration in distinct brain regions in each disease. Unlike many other polyglutamine proteins, whose functions are not yet fully understood, TBP is a well-characterized transcription factor that is restricted to the nucleus. Thus, investigating how mutant TBP mediates neuropathology should help elucidate the mechanisms by which transcriptional dysregulation contributes to neuronal dysfunction and/or neurodegeneration in polyglutamine diseases. To this end, we characterized cellular and mouse models expressing polyQ-expanded TBP. The cell model exhibits characteristic features of neuronal dysfunction, including decreased cell viability and defective neurite outgrowth. We found that the high-affinity nerve growth factor receptor, TrkA, is down-regulated by mutant TBP in cells. Down-regulation of TrkA also occurs in the cerebellum of SCA17 transgenic mice prior to Purkinje cell degeneration. Mutant TBP binds more Sp1, reduces its occupancy of the TrkA promoter and inhibits the activity of the TrkA promoter. These findings suggest that the transcriptional down-regulation of TrkA by mutant TBP contributes to SCA17 pathogenesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.