ArticleScientific reports2016
Transcriptional induction of the heat shock protein B8 mediates the clearance of misfolded proteins responsible for motor neuron diseases.
Article in Scientific reports, 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
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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, 96 citations in OpenAlex.
- Colchicine treatment in amyotrophic lateral sclerosis: safety, biological and clinical effects in a randomized clinical trial.Brain communications · 2024Trial
- Rest Induces a Distinct Transcriptional Program in the Nervous System of the ExercisedInternational journal of molecular sciences · 2025Article
- Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.Cells · 2025Review
- Unlocking Disease-Modifying Treatments for TDP-43-Mediated Neurodegeneration.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The Spectrum of Small Heat Shock Protein B8 (International journal of molecular sciences · 2025Review
- Small Heat Shock Proteins: Protein Aggregation Amelioration and Neuro- and Age-Protective Roles.International journal of molecular sciences · 2025Review
- Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.Nature reviews. Neurology · 2025Review
- Small HSPs at the crossroad between protein aggregation, autophagy and unconventional secretion: clinical implications and potential therapeutic opportunities in the context of neurodegenerative diseases.Frontiers in cell and developmental biology · 2025Review
- Targeting Protein Aggregation in ALS.Biomolecules · 2024Review
- A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling.Cell death discovery · 2023Article
- Roles of Stress Response in Autophagy Processes and Aging-Related Diseases.International journal of molecular sciences · 2023Review
- The HSPB1-p62/SQSTM1 functional complex regulates the unconventional secretion and transcellular spreading of the HD-associated mutant huntingtin protein.Human molecular genetics · 2023Article
- Article
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
- The role of autophagy-lysosomal pathway in motor neuron diseases.Biochemical Society transactions · 2022Review
- The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases.International journal of molecular sciences · 2022Review
- Emerging Therapies and Novel Targets for TDP-43 Proteinopathy in ALS/FTD.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
- Article
- Review
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 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurodegenerative diseases (NDs) are often associated with the presence of misfolded protein inclusions. The chaperone HSPB8 is upregulated in mice, the human brain and muscle structures affected during NDs progression. HSPB8 exerts a potent pro-degradative activity on several misfolded proteins responsible for familial NDs forms. Here, we demonstrated that HSPB8 also counteracts accumulation of aberrantly localized misfolded forms of TDP-43 and its 25 KDa fragment involved in most sporadic cases of Amyotrophic Lateral Sclerosis (sALS) and of Fronto Lateral Temporal Dementia (FLTD). HSPB8 acts with BAG3 and the HSP70/HSC70-CHIP complex enhancing the autophagic removal of misfolded proteins. We performed a high-through put screening (HTS) to find small molecules capable of inducing HSPB8 in neurons for therapeutic purposes. We identified two compounds, colchicine and doxorubicin, that robustly up-regulated HSPB8 expression. Both colchicine and doxorubicin increased the expression of the master regulator of autophagy TFEB, the autophagy linker p62/SQSTM1 and the autophagosome component LC3. In line, both drugs counteracted the accumulation of TDP-43 and TDP-25 misfolded species responsible for motoneuronal death in sALS. Thus, analogs of colchicine and doxorubicin able to induce HSPB8 and with better safety and tolerability may result beneficial in NDs models.
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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.