ArticleEMBO molecular medicine2022
The HSP40 chaperone Ydj1 drives amyloid beta 42 toxicity.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
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- The Amyloid Plaque Proteomes of Alzheimer's Disease and Mild Cognitive Impairment.Research square · 2026Article
- A J-domain protein enhances memory by promoting physiological amyloid formation inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Understanding and improving vaccine efficacy in older adults.Nature aging · 2025Review
- DNAJA: emerging targets for anti-tumor therapy.Future oncology (London, England) · 2025Review
- Chaperone-mediated heterotypic phase separation regulates liquid-to-solid phase transitions of tau into amyloid fibrils.Science advances · 2025Article
- Blood biomarkers for vascular cognitive impairment based on neuronal function: a systematic review and meta-analysis.Frontiers in neurology · 2025Review
- Evaluating protein prenylation of human and viral CaaX sequences using a humanized yeast system.Disease models & mechanisms · 2024Article
- Mrj is a chaperone of the Hsp40 family that regulates Orb2 oligomerization and long-term memory in Drosophila.PLoS biology · 2024Article
- Identification of novel hub genes for Alzheimer's disease associated with the hippocampus using WGCNA and differential gene analysis.Frontiers in neuroscience · 2024Article
- A multi-layered network model identifies Akt1 as a common modulator of neurodegeneration.Molecular systems biology · 2023Article
- Telomeres: Dysfunction, Maintenance, Aging and Cancer.Aging and disease · 2023Review
- Simple model systems reveal conserved mechanisms of Alzheimer's disease and related tauopathies.Molecular neurodegeneration · 2023Review
- A Humanized Yeast System for Evaluating the Protein Prenylation of a Wide Range of Human and Viral CaaX Sequences.bioRxiv : the preprint server for biology · 2023Article
- Droj2 Facilitates Somatosensory Neurite Sculpting via GTP-Binding Protein Arf102F inInternational journal of molecular sciences · 2023Article
- Article
- Exploratory Assessment of Proteomic Network Changes in Cerebrospinal Fluid of Mild Cognitive Impairment Patients: A Pilot Study.Biomolecules · 2023Article
- Alzheimer's Disease: Significant Benefit from the Yeast-Based Models.International journal of molecular sciences · 2023Review
- Neurodegenerative disease-associated inclusion bodies are cleared by selective autophagy in budding yeast.Autophagy reports · 2023Article
- Lipid metabolism and ageing in Caenorhabditis elegans: a complex interplay.Biogerontology · 2022Review
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Authors and funding
40 authors at 8 institutions in 4 countries.
Funding
Abstract
Amyloid beta 42 (Abeta42) is the principal trigger of neurodegeneration during Alzheimer's disease (AD). However, the etiology of its noxious cellular effects remains elusive. In a combinatory genetic and proteomic approach using a yeast model to study aspects of intracellular Abeta42 toxicity, we here identify the HSP40 family member Ydj1, the yeast orthologue of human DnaJA1, as a crucial factor in Abeta42-mediated cell death. We demonstrate that Ydj1/DnaJA1 physically interacts with Abeta42 (in yeast and mouse), stabilizes Abeta42 oligomers, and mediates their translocation to mitochondria. Consequently, deletion of YDJ1 strongly reduces co-purification of Abeta42 with mitochondria and prevents Abeta42-induced mitochondria-dependent cell death. Consistently, purified DnaJ chaperone delays Abeta42 fibrillization in vitro, and heterologous expression of human DnaJA1 induces formation of Abeta42 oligomers and their deleterious translocation to mitochondria in vivo. Finally, downregulation of the Ydj1 fly homologue, Droj2, improves stress resistance, mitochondrial morphology, and memory performance in a Drosophila melanogaster AD model. These data reveal an unexpected and detrimental role for specific HSP40s in promoting hallmarks of Abeta42 toxicity.
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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 Socratic graph.