ArticlePloS one2012
Deletion of the BDNF truncated receptor TrkB.T1 delays disease onset in a mouse model of amyotrophic lateral sclerosis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions.Frontiers in neuroscience · 2022Pooled it
- Review
- Motor Neuron Size-Dependent Differences in mRNA Expression of Tropomyosin-Related Kinase Receptor B in Adult Rats.Journal of neurochemistry · 2026Article
- Review
- Syn3, a newly developed cyclic peptide and BDNF signaling enhancer, ameliorates retinal ganglion cell degeneration in diabetic retinopathy.Protein & cell · 2024Article
- Genetic Variations in TrkB.T1 Isoform and Their Association With Somatic and Psychological Symptoms in Individuals With IBS.The journal of pain · 2024Article
- Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.Neuroscience bulletin · 2024Review
- Targeting the postsynaptic scaffolding protein PSD-95 enhances BDNF signaling to mitigate depression-like behaviors in mice.Science signaling · 2024Article
- Distinct neuroinflammatory signatures exist across genetic and sporadic amyotrophic lateral sclerosis cohorts.Brain : a journal of neurology · 2023Article
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- Neurotrophic factors in the physiology of motor neurons and their role in the pathobiology and therapeutic approach to amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2023Review
- Amyotrophic Lateral Sclerosis Pathoetiology and Pathophysiology: Roles of Astrocytes, Gut Microbiome, and Muscle Interactions via the Mitochondrial Melatonergic Pathway, with Disruption by Glyphosate-Based Herbicides.International journal of molecular sciences · 2022Review
- BDNF-dependent modulation of axonal transport is selectively impaired in ALS.Acta neuropathologica communications · 2022Article
- The Role of Neurotrophin Signaling in Age-Related Cognitive Decline and Cognitive Diseases.International journal of molecular sciences · 2022Review
- Recent Advances on the Role of Brain-Derived Neurotrophic Factor (BDNF) in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Article
- Human-Induced Pluripotent Stem Cell-Based Models for Studying Sex-Specific Differences in Neurodegenerative Diseases.Advances in experimental medicine and biology · 2022Review
- Emerging roles of dysregulated adenosine homeostasis in brain disorders with a specific focus on neurodegenerative diseases.Journal of biomedical science · 2021Review
- How Are Adenosine and Adenosine ABiomedicines · 2021Review
- Delayed onset of inherited ALS by deletion of the BDNF receptor TrkB.T1 is non-cell autonomous.Experimental neurology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Brain Derived Neurotrophic Factor (BDNF) exerts strong pro-survival effects on developing and injured motoneurons. However, in clinical trials, BDNF has failed to benefit patients with amyotrophic lateral sclerosis (ALS). To date, the cause of this failure remains unclear. Motoneurons express the TrkB kinase receptor but also high levels of the truncated TrkB.T1 receptor isoform. Thus, we investigated whether the presence of this receptor may affect the response of diseased motoneurons to endogenous BDNF. We deleted TrkB.T1 in the hSOD1(G93A) ALS mouse model and evaluated the impact of this mutation on motoneuron death, muscle weakness and disease progression. We found that TrkB.T1 deletion significantly slowed the onset of motor neuron degeneration. Moreover, it delayed the development of muscle weakness by 33 days. Although the life span of the animals was not affected we observed an overall improvement in the neurological score at the late stage of the disease. To investigate the effectiveness of strategies aimed at bypassing the TrkB.T1 limit to BDNF signaling we treated SOD1 mutant mice with the adenosine A2A receptor agonist CGS21680, which can activate motoneuron TrkB receptor signaling independent of neurotrophins. We found that CGS21680 treatment slowed the onset of motor neuron degeneration and muscle weakness similarly to TrkB.T1 removal. Together, our data provide evidence that endogenous TrkB.T1 limits motoneuron responsiveness to BDNF in vivo and suggest that new strategies such as Trk receptor transactivation may be used for therapeutic intervention in ALS or other neurodegenerative disorders.
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.