ArticleProceedings of the National Academy of Sciences of the United States of America2016
TRiC subunits enhance BDNF axonal transport and rescue striatal atrophy in Huntington's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 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
59 citing papers in PubMed, 97 citations in OpenAlex.
- Molecular architects of memory: BDNF/TrkB signaling and trafficking in neuronal plasticity and memory.Molecular psychiatry · 2026Review
- Huntingtin polyglutamine expansions misdirect axonal transport by perturbing motor and adaptor recruitment.iScience · 2026Article
- Chaperonin in health and disease.Molecular biomedicine · 2026Review
- Huntingtin and its allies at the cortico-striatal synapse.Cell death & disease · 2026Review
- Inhba, Homer1 and Bdnf are major targets of transcriptomic dysregulation by neurodegenerative disease-associated excitotoxic NMDA receptor signaling.Communications biology · 2025Article
- Exploring the potential role of microtubule associated proteins-2 in the pathogenesis of HIV associated neurocognitive disorders.Neurotoxicity research · 2025Review
- Aged hippocampal single-cell atlas screening unveils disrupted neuroglial system in postoperative cognitive impairment.Aging cell · 2025Article
- Brain-Derived Neurotrophic Factor (BDNF) in Huntington's Disease: Neurobiology and Therapeutic Potential.Current neuropharmacology · 2025Review
- CCT and Cullin1 Regulate the TORC1 Pathway to Promote Dendritic Arborization in Health and Disease.Cells · 2024Article
- BDNF and TRiC-inspired reagent rescue cortical synaptic deficits in a mouse model of Huntington's disease.Neurobiology of disease · 2024Article
- Neuropathogenesis-on-chips for neurodegenerative diseases.Nature communications · 2024Review
- Revisiting the chaperonin T-complex protein-1 ring complex in human health and disease: A proteostasis modulator and beyond.Clinical and translational medicine · 2024Review
- Loss of the E3 ubiquitin ligase TRIM67 alters the post-synaptic density proteome.bioRxiv : the preprint server for biology · 2024Article
- Loss of the E3 ubiquitin ligase TRIM67 alters the post-synaptic density proteome.microPublication biology · 2024Article
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- Keeping It Organized: Multicompartment Constructs to Mimic Tissue Heterogeneity.Advanced healthcare materials · 2023Review
- Overexpression of alpha synuclein disrupts APP and Endolysosomal axonal trafficking in a mouse model of synucleinopathy.Neurobiology of disease · 2023Article
- How Organ-on-a-Chip Technology Can Assist in Studying the Role of the Glymphatic System in Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Failure to Thrive: Impaired BDNF Transport along the Cortical-Striatal Axis in Mouse Q140 Neurons of Huntington's Disease.Biology · 2023Article
- Implications of Tau Dysregulation in Huntington's Disease and Potential for New Therapeutics.Journal of Huntington's disease · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Corticostriatal atrophy is a cardinal manifestation of Huntington's disease (HD). However, the mechanism(s) by which mutant huntingtin (mHTT) protein contributes to the degeneration of the corticostriatal circuit is not well understood. We recreated the corticostriatal circuit in microfluidic chambers, pairing cortical and striatal neurons from the BACHD model of HD and its WT control. There were reduced synaptic connectivity and atrophy of striatal neurons in cultures in which BACHD cortical and striatal neurons were paired. However, these changes were prevented if WT cortical neurons were paired with BACHD striatal neurons; synthesis and release of brain-derived neurotrophic factor (BDNF) from WT cortical axons were responsible. Consistent with these findings, there was a marked reduction in anterograde transport of BDNF in BACHD cortical neurons. Subunits of the cytosolic chaperonin T-complex 1 (TCP-1) ring complex (TRiC or CCT for chaperonin containing TCP-1) have been shown to reduce mHTT levels. Both CCT3 and the apical domain of CCT1 (ApiCCT1) decreased the level of mHTT in BACHD cortical neurons. In cortical axons, they normalized anterograde BDNF transport, restored retrograde BDNF transport, and normalized lysosomal transport. Importantly, treating BACHD cortical neurons with ApiCCT1 prevented BACHD striatal neuronal atrophy by enhancing release of BDNF that subsequently acts through tyrosine receptor kinase B (TrkB) receptor on striatal neurons. Our findings are evidence that TRiC reagent-mediated reductions in mHTT enhanced BDNF delivery to restore the trophic status of BACHD striatal neurons.
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.