ReviewThe Journal of biological chemistry2022
Folding or holding?-Hsp70 and Hsp90 chaperoning of misfolded proteins in neurodegenerative disease.
Review in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 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
67 citing papers in PubMed, 100 citations in OpenAlex.
- AHA1 Regulates Aβ Production via Modulation of APP Abundance and γ-Secretase Assembly.Journal of neurochemistry · 2026Article
- Beyond the structure-function paradigm: A comprehensive review of intrinsically disordered proteins.Biochemistry and biophysics reports · 2026Review
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Uremic Serum Alters Gene Expression Profiles and Signaling Pathway Activity in Porcine Arterial Smooth Muscle Cells.Biomolecules · 2026Article
- Network Biology of Alzheimer's Disease and Related Neurodegenerative Disorders: Molecular Mechanisms and Therapeutic Strategies.Biomolecules · 2026Review
- Chaperone proteins protect against desmin fragment amyloid aggregation.Biophysical journal · 2026Article
- A Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimer's and Parkinson's Disease.Journal of molecular neuroscience : MN · 2026Review
- Conserved Pathways, Divergent Outcomes: A Cross-Species Genomic Perspective on the Cancer-Neurodegeneration Paradox.International journal of molecular sciences · 2026Review
- Evolutionary remodeling of a remnant GET pathway factor into PEX38, an essential peroxin.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Breaking barriers: transitioning from X-ray crystallography to cryo-EM for structural studies.Acta crystallographica. Section D, Structural biology · 2026Article
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- Heat shock proteins in male infertility: recent advances and clinical implications.Frontiers in cell and developmental biology · 2026Review
- STIP1/HOP promotes the formation of cytotoxic α-synuclein oligomers.Molecular neurodegeneration advances · 2026Article
- Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential.Frontiers in aging neuroscience · 2026Review
- Intracellular aggregation of the transthyretin protein is limited by Hsp70 chaperones.bioRxiv : the preprint server for biology · 2025Article
- Effects of initial periodontal treatment on heat shock protein 90 and Interleukin-1β levels in gingival crevicular fluid of stage III periodontitis patients.BMC oral health · 2025Article
- Breaking Barriers: Transitioning from X-ray Crystallography to Cryo-EM for Structural Studies of ATAD2B.bioRxiv : the preprint server for biology · 2025Article
- Synthetic chaperone based on Hsp90-Tau interaction inhibits Tau aggregation and rescues physiological Tau-Microtubule interaction.Nature communications · 2025Article
- LAMP5 modulates IRF4 stability and nuclear transport: a critical mechanism in myeloma progression and therapy.Oncogene · 2025Article
7 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The toxic accumulation of misfolded proteins as inclusions, fibrils, or aggregates is a hallmark of many neurodegenerative diseases. However, how molecular chaperones, such as heat shock protein 70 kDa (Hsp70) and heat shock protein 90 kDa (Hsp90), defend cells against the accumulation of misfolded proteins remains unclear. The ATP-dependent foldase function of both Hsp70 and Hsp90 actively transitions misfolded proteins back to their native conformation. By contrast, the ATP-independent holdase function of Hsp70 and Hsp90 prevents the accumulation of misfolded proteins. Foldase and holdase functions can protect against the toxicity associated with protein misfolding, yet we are only beginning to understand the mechanisms through which they modulate neurodegeneration. This review compares recent structural findings regarding the binding of Hsp90 to misfolded and intrinsically disordered proteins, such as tau, α-synuclein, and Tar DNA-binding protein 43. We propose that Hsp90 and Hsp70 interact with these proteins through an extended and dynamic interface that spans the surface of multiple domains of the chaperone proteins. This contrasts with many other Hsp90-client protein interactions for which only a single bound conformation of Hsp90 is proposed. The dynamic nature of these multidomain interactions allows for polymorphic binding of multiple conformations to vast regions of Hsp90. The holdase functions of Hsp70 and Hsp90 may thus allow neuronal cells to modulate misfolded proteins more efficiently by reducing the long-term ATP running costs of the chaperone budget. However, it remains unclear whether holdase functions protect cells by preventing aggregate formation or can increase neurotoxicity by inadvertently stabilizing deleterious oligomers.
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.