ArticlePLoS biology2017
Human cyclophilin 40 unravels neurotoxic amyloids.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Proline/sidechain C-H/O interactions stabilizePhysical chemistry chemical physics : PCCP · 2026Article
- Broken but not beaten: Challenge of reducing the amyloids pathogenicity by degradation.Journal of advanced research · 2025Review
- Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity.Nature cell biology · 2025Article
- The role of the FKBP51-Hsp90 complex in Alzheimer's disease: An emerging new drug target.Cell stress & chaperones · 2024Review
- "Cyclophilin A" Enzymatic Effect on the Aggregation Behavior of 1N4R Tau Protein: An Overlooked Crucial Determinant that should be Re-considered in Alzheimer's Disease Pathogenesis.Current Alzheimer research · 2024Article
- Insights into Hsp90 mechanism andFrontiers in molecular biosciences · 2024Review
- DnaJs are enriched in tau regulators.International journal of biological macromolecules · 2023Article
- Tau-RNA complexes inhibit microtubule polymerization and drive disease-relevant conformation change.Brain : a journal of neurology · 2023Article
- The Crystal Structure of the Hsp90-LA1011 Complex and the Mechanism by Which LA1011 May Improve the Prognosis of Alzheimer's Disease.Biomolecules · 2023Article
- Article
- Early-Stage Oligomerization of Prion-like Polypeptides Reveals the Molecular Mechanism of Amyloid-Disrupting Capacity by Proline Residues.The journal of physical chemistry. B · 2023Article
- Chaperoning of specific tau structure by immunophilin FKBP12 regulates the neuronal resilience to extracellular stress.Science advances · 2023Article
- Reversible protein assemblies in the proteostasis network in health and disease.Frontiers in molecular biosciences · 2023Review
- Amyloid Disassembly: What Can We Learn from Chaperones?Biomedicines · 2022Review
- Chaperoning activity of the cyclophilin family prevents tau aggregation.Protein science : a publication of the Protein Society · 2022Article
- Peptidyl Prolyl Isomerase A Modulates the Liquid-Liquid Phase Separation of Proline-Rich IDPs.Journal of the American Chemical Society · 2022Article
- Molecular mechanisms of amyloid disaggregation.Journal of advanced research · 2022Review
- Accumulation of C-terminal cleaved tau is distinctly associated with cognitive deficits, synaptic plasticity impairment, and neurodegeneration in aged mice.GeroScience · 2022Article
- Nuclear-Import Receptors Counter Deleterious Phase Transitions in Neurodegenerative Disease.Journal of molecular biology · 2022Review
- Small Heat Shock Protein 22 Improves Cognition and Learning in the Tauopathic Brain.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
The accumulation of amyloidogenic proteins is a pathological hallmark of neurodegenerative disorders. The aberrant accumulation of the microtubule associating protein tau (MAPT, tau) into toxic oligomers and amyloid deposits is a primary pathology in tauopathies, the most common of which is Alzheimer's disease (AD). Intrinsically disordered proteins, like tau, are enriched with proline residues that regulate both secondary structure and aggregation propensity. The orientation of proline residues is regulated by cis/trans peptidyl-prolyl isomerases (PPIases). Here we show that cyclophilin 40 (CyP40), a PPIase, dissolves tau amyloids in vitro. Additionally, CyP40 ameliorated silver-positive and oligomeric tau species in a mouse model of tau accumulation, preserving neuronal health and cognition. Nuclear magnetic resonance (NMR) revealed that CyP40 interacts with tau at sites rich in proline residues. CyP40 was also able to interact with and disaggregate other aggregating proteins that contain prolines. Moreover, CyP40 lacking PPIase activity prevented its capacity for disaggregation in vitro. Finally, we describe a unique structural property of CyP40 that may permit disaggregation to occur in an energy-independent manner. This study identifies a novel human protein disaggregase and, for the first time, demonstrates its capacity to dissolve intracellular amyloids.
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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.