ArticleHuman molecular genetics2016
The chaperone HSPB8 reduces the accumulation of truncated TDP-43 species in cells and protects against TDP-43-mediated toxicity.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03693781 (Colchicine for Amyotrophic Lateral Sclerosis), which is not on this map. Cited by 61 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.
Colchicine for Amyotrophic Lateral Sclerosis: a Phase II, Randomized, Double Blind, Placebo Controlled, Multicenter Clinical Trial
Who cites it
61 citing papers in PubMed, 90 citations in OpenAlex.
- Colchicine treatment in amyotrophic lateral sclerosis: safety, biological and clinical effects in a randomized clinical trial.Brain communications · 2024Trial
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- VAPB confers selective neuroprotection by driving autophagic degradation of pathogenic aggregates in ALS.Acta neuropathologica communications · 2026Article
- Small heat shock protein HSPB8 interacts with a pre-fibrillar TDP43 low complexity domain species to delay fibril formation.Biophysical chemistry · 2026Article
- Proteostasis network response to environmental chronic stress: linking survival to protein aggregation in a human neuroblastoma cellular model.Cellular and molecular life sciences : CMLS · 2025Article
- TRAF6 regulates ubiquitination-independent TDP-43 condensation and related neurodegeneration.Molecular psychiatry · 2025Article
- Regulation of physiological and pathological condensates by molecular chaperones.The FEBS journal · 2025Review
- Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.Nature reviews. Neurology · 2025Review
- TDP-43 as a potential retinal biomarker for neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Silencing miR-126-5p protects trabecular meshwork cells against chronic oxidative injury by upregulating HSPB8 to activate PI3K/AKT pathway.Journal of molecular histology · 2024Article
- Targeting Protein Aggregation in ALS.Biomolecules · 2024Review
- Aberrant protein aggregation in amyotrophic lateral sclerosis.Journal of neurology · 2024Review
- Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.Annals of clinical and translational neurology · 2023Review
- HSPB8 frameshift mutant aggregates weaken chaperone-assisted selective autophagy in neuromyopathies.Autophagy · 2023Article
- Article
- Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders.Frontiers in molecular neuroscience · 2023Review
- Review
- Molecular Investigations of Protein Aggregation in the Pathogenesis of Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
- TDP-35, a truncated fragment of TDP-43, induces dose-dependent toxicity and apoptosis in flies.Neural regeneration research · 2022Article
- The role of autophagy-lysosomal pathway in motor neuron diseases.Biochemical Society transactions · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
Aggregation of TAR-DNA-binding protein 43 (TDP-43) and of its fragments TDP-25 and TDP-35 occurs in amyotrophic lateral sclerosis (ALS). TDP-25 and TDP-35 act as seeds for TDP-43 aggregation, altering its function and exerting toxicity. Thus, inhibition of TDP-25 and TDP-35 aggregation and promotion of their degradation may protect against cellular damage. Upregulation of HSPB8 is one possible approach for this purpose, since this chaperone promotes the clearance of an ALS associated fragments of TDP-43 and is upregulated in the surviving motor neurones of transgenic ALS mice and human patients. We report that overexpression of HSPB8 in immortalized motor neurones decreased the accumulation of TDP-25 and TDP-35 and that protection against mislocalized/truncated TDP-43 was observed for HSPB8 in Drosophila melanogaster Overexpression of HSP67Bc, the functional ortholog of human HSPB8, suppressed the eye degeneration caused by the cytoplasmic accumulation of a TDP-43 variant with a mutation in the nuclear localization signal (TDP-43-NLS). TDP-43-NLS accumulation in retinal cells was counteracted by HSP67Bc overexpression. According with this finding, downregulation of HSP67Bc increased eye degeneration, an effect that is consistent with the accumulation of high molecular weight TDP-43 species and ubiquitinated proteins. Moreover, we report a novel Drosophila model expressing TDP-35, and show that while TDP-43 and TDP-25 expression in the fly eyes causes a mild degeneration, TDP-35 expression leads to severe neurodegeneration as revealed by pupae lethality; the latter effect could be rescued by HSP67Bc overexpression. Collectively, our data demonstrate that HSPB8 upregulation mitigates TDP-43 fragment mediated toxicity, in mammalian neuronal cells and flies.
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.