ArticleProceedings of the National Academy of Sciences of the United States of America2016
Holdase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity in Drosophila.
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 36 papers.
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Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- Differential expression of neuronal function genes follows a tissue-specific temporal dynamic during Deformed Wing Virus infection in honeybees.Scientific reports · 2026Article
- Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structures of the 26Science advances · 2026Article
- Co-chaperones fine-tune the function of heat shock protein 70 (Hsp70), whether to fold, hold, or degrade substrates in ensuring cellular protein homeostasis.Journal of biosciences · 2025Review
- Article
- Protein retention in the endoplasmic reticulum rescues Aβ toxicity in Drosophila.Neurobiology of aging · 2023Article
- Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity.Molecular neurodegeneration · 2023Article
- Nuclear import receptors are recruited by FG-nucleoporins to rescue hallmarks of TDP-43 proteinopathy.Molecular neurodegeneration · 2022Article
- Clearance of variant Creutzfeldt-Jakob disease prions in vivo by the Hsp70 disaggregase system.Brain : a journal of neurology · 2022Article
- The Mitochondrial HSP90 Paralog TRAP1: Structural Dynamics, Interactome, Role in Metabolic Regulation, and Inhibitors.Biomolecules · 2022Review
- Parkinson's Disease-Specific Autoantibodies against the Neuroprotective Co-Chaperone STIP1.Cells · 2022Article
- Extracellular HSPs: The Potential Target for Human Disease Therapy.Molecules (Basel, Switzerland) · 2022Review
- Is Protein Folding a Thermodynamically Unfavorable, Active, Energy-Dependent Process?International journal of molecular sciences · 2022Review
- Hsp70 Inhibits Aggregation of IAPP by Binding to the Heterogeneous Prenucleation Oligomers.Biophysical journal · 2021Article
- Proteostasis-associated aging: lessons from a Drosophila model.Genes & genomics · 2021Review
- Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers.International journal of molecular sciences · 2020Review
- HSP70 regulates Eg5 distribution within the mitotic spindle and modulates the cytotoxicity of Eg5 inhibitors.Cell death & disease · 2020Article
- Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-β deposition in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2020Article
- Functional diversity between HSP70 paralogs caused by variable interactions with specific co-chaperones.The Journal of biological chemistry · 2020Article
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8 authors at 1 institution in 1 country.
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Abstract
Alzheimer's disease (AD) is the most prevalent of a large group of related proteinopathies for which there is currently no cure. Here, we used Drosophila to explore a strategy to block Aβ42 neurotoxicity through engineering of the Heat shock protein 70 (Hsp70), a chaperone that has demonstrated neuroprotective activity against several intracellular amyloids. To target its protective activity against extracellular Aβ42, we added a signal peptide to Hsp70. This secreted form of Hsp70 (secHsp70) suppresses Aβ42 neurotoxicity in adult eyes, reduces cell death, protects the structural integrity of adult neurons, alleviates locomotor dysfunction, and extends lifespan. SecHsp70 binding to Aβ42 through its holdase domain is neuroprotective, but its ATPase activity is not required in the extracellular space. Thus, the holdase activity of secHsp70 masks Aβ42 neurotoxicity by promoting the accumulation of nontoxic aggregates. Combined with other approaches, this strategy may contribute to reduce the burden of AD and other extracellular proteinopathies.
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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.