HSP90-Tau Disaggregation Complex Enhancement
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From Analysis:
Tau propagation mechanisms and therapeutic interception points
Investigate prion-like spreading of tau pathology through connected brain regions, focusing on trans-synaptic transfer, extracellular vesicle-mediated spread, and intervention strategies at each propagation step
Description
Molecular Mechanism and Rationale
The heat shock protein 90 (HSP90) chaperone system represents a critical cellular machinery for protein folding, stability, and quality control. HSP90AA1, the inducible cytoplasmic isoform of HSP90, exhibits distinct conformational states that can be allosterically modulated to enhance specific client protein interactions. In the context of tau pathology, HSP90 demonstrates intrinsic disaggregation activity toward tau aggregates through a complex mechanism involving ATP-dependent conformational cycling and co-chaperone recruitment.
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Curated Mechanism Pathway
Curated pathway diagram from expert analysis
graph TD
subgraph "Tau Pathology"
A["Tau Aggregates"]
B["Misfolded Tau"]
end
subgraph "HSP90 System"
C["HSP90AA1"]
D["ATP Binding Domain"]
E["Allosteric Binding Pocket"]
F["Co-chaperones"]
end
subgraph "Therapeutic Intervention"
G["Allosteric Modulators"]
H["Enhanced Conformation"]
I["ATP-dependent Cycling"]
end
subgraph "Cellular Outcomes"
J["Disaggregation Complex"]
K["Tau Clearance"]
L["Protein Quality Control"]
M["Neuronal Protection"]
end
N["Conformational States"]
O["Client Protein Interaction"]
A -->|"accumulation"| B
B -->|"targets"| C
G -->|"binds to"| E
E -->|"modulates"| C
C -->|"contains"| D
C -->|"recruits"| F
G -->|"induces"| H
H -->|"enables"| I
C -->|"adopts"| N
N -->|"enhances"| O
F -->|"forms"| J
I -->|"drives"| J
J -->|"promotes"| K
K -->|"improves"| L
L -->|"leads to"| M
style A fill:#ff9999
style M fill:#99ff99
style G fill:#9999ff
GTEx v10 Brain Expression
JSONMedian TPM across 13 brain regions for HSP90AA1 from GTEx v10.
Dimension Scores
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✓ Supporting Evidence 20
This work provides a quantitative kinetic analysis of oxidative pathways involving linoleic acid and the common dietary antioxidant quercetin (flavonoid), both bound to human serum albumin (HSA). In particular, it is shown that quercetin, although embedded in drug site I, is oxidized as quickly as free quercetin under a flux of hydrophilic peroxyl radicals. This observation suggests that efficient charge relays are established between the periphery of HSA and bound quercetin. Moreover, the peroxidation of HSA-bound linoleic acid is shown to take place at some specific fatty acid binding sites once one to two critical HSA residues are themselves oxidized. Quercetin efficiently delays the onset of lipid peroxidation. The inhibition persists long after the total consumption of quercetin, in agreement with some quercetin oxidation products exerting a residual antioxidant activity. Consistently, HSA markedly increases the maximal concentration of a two-electron oxidation product of querceti
There is an urgent need to develop the next-generation vectors for gene therapy of muscle disorders, given the relatively modest advances in clinical trials. These vectors should express substantially higher levels of the therapeutic transgene, enabling the use of lower and safer vector doses. In the current study, we identify potent muscle-specific transcriptional cis-regulatory modules (CRMs), containing clusters of transcription factor binding sites, using a genome-wide data-mining strategy. These novel muscle-specific CRMs result in a substantial increase in muscle-specific gene transcription (up to 400-fold) when delivered using adeno-associated viral vectors in mice. Significantly higher and sustained human micro-dystrophin and follistatin expression levels are attained than when conventional promoters are used. This results in robust phenotypic correction in dystrophic mice, without triggering apoptosis or evoking an immune response. This multidisciplinary approach has potential
HSP90 co-chaperones FKBP51 and FKBP52 differentially regulate tau aggregation, with FKBP52 promoting disaggreg… 0.76▼
Mitochondrial production of superoxide and hydrogen peroxide is potentially important in cell signaling and disease. Eleven distinct mitochondrial sites that differ markedly in capacity are known to leak electrons to oxygen to produce O2̇̄ and/or H2O2 We discuss their contributions to O2̇̄/H2O2 production under native conditions in mitochondria oxidizing different substrates and in conditions mimicking physical exercise and the changes in their capacities after caloric restriction. We review the use of S1QELs and S3QELs, suppressors of mitochondrial O2̇̄/H2O2 generation that do not inhibit oxidative phosphorylation, as tools to characterize the contributions of specific sites in situ and in vivo.
Pharmacological activation of HSP90 ATPase activity with celastrol reduces tau pathology and improves cognitiv… 0.88▼
Accurate forecasting is required to measure future national energy performance levels in order to establish clear policies for both monitoring and reducing Nitrous Oxide and other harmful emissions. Using the well-established and accepted measures, we predict the Nitrous Oxide emissions for the year 2030 based on actual data from the years 2000 to 2016 for six countries responsible for 61% of global emissions (China, Indonesia, India, Japan, Russia and the USA). Three advanced mathematical grey predictions models were employed, namely the Even Grey Model (1, 1), the Discrete Grey Model (1, 1) and the Non-homogeneous Discrete Grey Model, which is capable of working with poor or limited data. Results showed that the Non-homogeneous Discrete Grey Model was a better fit and proved more effective in forecasting Nitrous Oxide emissions because it produced the lowest mean absolute percentage error for all countries when compared to the Even Grey Model (1, 1) and the Discrete Grey Model (1, 1)
HSP90 complexes with BAG-1 and HSP70 form a coordinated disaggregase machinery that effectively solubilizes ta… 0.91▼
Overexpression of HSP90AA1 in hippocampal neurons reduces tau hyperphosphorylation and restores synaptic plast… 0.84▼
The lack of data outsourcing in healthcare management systems slows down the intercommunication and information sharing between different entities. A standard solution is outsourcing the electronic health record (EHR) to a cloud service provider (CSP). The outsourcing of the EHR should be performed securely without compromising the CSP functionalities. Searchable encryption would be a viable approach to ensure the confidentiality of the data without compromising searchability and accessibility. However, most existing searchable encryption solutions use centralised architecture. These systems have trust issues as not all the CSPs are fully trusted or honest. To address these problems, we explore blockchain technology with smart contract applications to construct a decentralised system with auditable yet immutable data storage and access. First, we propose a blockchain-based searchable encryption scheme for EHR storage and updates in a decentralised fashion. The proposed scheme supports
Explore the mechanism and substance basis of Mahuang FuziXixin Decoction for the treatment of lung cancer base… MEDIUM▼
BACKGROUND: Mahuang FuziXixin Decoction (MFXD) is a classic Chinese herbal formula for the treatment of lung cancer. However, its mechanisms of action are unclear. In present study, network pharmacology and molecular docking technology were employed to investigate the molecular mechanism and substance basis of MFXD for the treatment of lung cancer. METHOD: The active compounds and corresponding targets of MFXD were collected through the TCMSP database. OMIM and GeneCards databases were applied to filter the targets of lung cancer. The protein-protein interaction (PPI) were acquired through the STRING platform. Metascape and the Bioinformatics server were used for the visualization of GO and KEGG analysis. The tissue and organ distribution of targets was evaluated based on the BioGPS database. The binding affinity between potential targets and active compounds was evaluated by molecular docking. RESULT: A total of 51 active compounds and 118 targets of MFXD were collected. The target wi
Paeoniflorin protects against cisplatin-induced acute kidney injury through targeting Hsp90AA1-Akt protein-pro… MEDIUM▼
ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall has been used in Chinese Medicine for thousands of years, especially having anti-inflammatory, sedative, analgesic and other ethnic pharmacological effects. Moreover, Paeoniflorin is the main active ingredient of the Paeonia lactiflora Pall, and most are used in the treatment of inflammation-related autoimmune diseases. In recent years, studies have found that Paeoniflorin has a therapeutic effect on a variety of kidney diseases. AIM OF THE STUDY: Cisplatin (CIS) is limited in clinical use due to its serious side effects, such as renal toxicity, and there is no effective method for prevention. Paeoniflorin (Pae) is a natural polyphenol which has a protective effect against many kidney diseases. Therefore, our study is to explore the effect of Pae on CIS-induced AKI and the specific mechanism. MATERIALS AND METHODS: Firstly, CIS induced acute renal injury model was constructed in vivo and in vitro, and Pae was continuously injected
A novel MTORC2-AKT-ROS axis triggers mitofission and mitophagy-associated execution of colorectal cancer cells… MEDIUM▼
RAS is one of the most commonly mutated oncogenes associated with multiple cancer hallmarks. Notably, RAS activation induces intracellular reactive oxygen species (ROS) generation, which we previously demonstrated as a trigger for autophagy-associated execution of mutant KRAS-expressing cancer cells. Here we report that drug (merodantoin; C1)-induced activation of mutant KRAS promotes phospho-AKT S473-dependent ROS-mediated S616 phosphorylation and mitochondrial localization of DNM1L/DRP1 (dynamin 1 like) and cleavage of the fusion-associated protein OPA1 (OPA1 mitochondrial dynamin like GTPase). Interestingly, accumulation of the outer mitochondrial membrane protein VDAC1 (voltage dependent anion channel 1) is observed in mutant KRAS-expressing cells upon exposure to C1. Conversely, silencing VDAC1 abolishes C1-induced mitophagy, and gene knockdown of either KRAS, AKT or DNM1L rescues ROS-dependent VDAC1 accumulation and stability, thus suggesting an axis of mutant active KRAS-phospho
Network pharmacology and molecular docking combined with widely targeted metabolomics to elucidate the potenti… MEDIUM▼
BACKGROUND: The whole herb of Euphorbia helioscopia has been traditionally used for treating pulmonary tuberculosis, malaria, warts, lung cancer and bacillary dysentery for a long time in China. However, E. helioscopia seeds are often discarded and its medicinal value is often ignored, resulting in a waste of resources. METHOD: In this work, widely targeted metabolomics based on UPLC-ESI-QTRAP-MS/MS methods and metware database (MWDB) were firstly used to identify the chemical compositions of EHS. Besides, network pharmacology, molecular docking and molecular dynamics simulation were performed for elucidating the potential compounds and targets of E. helioscopia seeds for the treatment of pulmonary fibrosis via common database (like TCMSP, Genecards, DAVID, STRING) and common software (like Sybyl, Cytoscape, Pymol and Schrödinger). RESULT: The results of widely targeted metabolomics showed 231 compounds including 12 categories were identified. The highest content compositions are lipid
Network Pharmacology-Based Strategy Combined with Molecular Docking and in vitro Validation Study to Explore t… MEDIUM▼
BACKGROUND: Huo Luo Xiao Ling Dan (HLXLD), a famous Traditional Chinese Medicine (TCM) classical formula, possesses anti-atherosclerosis (AS) activity. However, the underlying molecular mechanisms remain obscure. AIM: The network pharmacology approach, molecular docking strategy, and in vitro validation experiment were performed to explore the potential active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS. METHODS: Several public databases were used to search for active components and targets of HLXLD, as well as AS-related targets. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis. Subsequently, the molecular docking strategy and molecular dynamics simulation were carried out to predict the affinity and stability of active compounds and key targets. In vitro cell experiment was performed to verify the findings from bioinformatics analysis. RESULTS: A tota
UNLABELLED: Acarbose is an α-glucosidase inhibitor that helps lower blood sugar after meals by stopping complex carbohydrates from turning into simple sugars; however, its role other than α-glucosidase inhibition is not yet fully understood. In this study, we used bioinformatics to explore the molecular targets and mechanisms of acarbose in type 2 diabetes (T2D). We found one hundred and twenty-seven shared targets between proteins linked to acarbose and genes related to T2D. Analysis showed these targets are mainly involved in insulin signaling, glucose metabolism, PI3K/Akt pathway, and inflammation. Network analysis highlighted 10 important genes: AKT1, ALB, EGFR, ESR1, GSK3B, HSP90AA1, PPARG, STAT3, SRC, and TNF. Expression profiling showed these genes have different patterns in various tissues from diabetic samples. Molecular docking results indicated a binding affinity of acarbose with the key proteins, with EGFR showing the lowest binding energy of - 7.8 kcal/mol. Molecular dynam
A Study on the Mechanism of Acetyl Tributyl Citrate-Induced Infertility Toxicity and the Protective Action of … MEDIUM▼
Infertility is a prevalent clinical issue which disrupts normal human life and exerts an impact on fertility rates within the population. The increase in environmental pollutants, including acetyl tributyl citrate (ATBC), has given rise to concerns regarding their potential toxicity in infertility-related disorders. Icariin exhibits therapeutic effects on infertility, yet its mechanism of action against plasticiser-induced reproductive disorders remains unclear. This study aims to elucidate the potential toxicological targets and molecular mechanisms of ATBC-induced infertility, as well as the therapeutic targets and mechanisms of icariin in treating ATBC-induced reproductive disorders, through network toxicology, molecular-docking techniques and molecular dynamics simulation. Utilising the component-target database SwissTargetPrediction, the Similarity Ensemble Approach, PharmMapper, the ChEMBL database, and disease databases including the Therapeutic Target Database, OMIM, GeneCards,
Chronic Thermal Stress During Early Zebrafish (Danio rerio) Development Induces Morphological, Molecular, and … MEDIUM▼
Temperature is a critical abiotic factor mediating the physiological fitness of fish. While the impact of acute high-temperature exposure is well documented in teleost fishes, the effects of chronic thermal stress, especially during early stages, remain poorly understood. This study examined the effects of prolonged exposure to elevated temperatures (34 ºC) on zebrafish (Danio rerio) development, survival, molecular responses and liver histology during pre-independent (24-120 h post fertilisation [hpf]) and independently feeding (240-480 hpf) stages. While survival was not affected by elevated temperature, normal development was significantly impaired in both stages. Compared to control conditions (28 °C), heat exposure (34 ºC) increased the incidence of deformities, including spinal and yolk sac abnormalities during the pre-independent feeding stage, and spinal and growth-related deformities during independent feeding. Heat-induced changes in gene expression were most evident during i
Elucidating the mechanisms of aristolochic acid-induced upper tract urothelial carcinoma: A multi-omics approa… MEDIUM▼
Aristolochic acids (AAs) are established human carcinogens strongly associated with upper tract urothelial carcinoma (UTUC). However, the multi-target oncogenic network beyond their genotoxic mechanism remains incompletely elucidated. This study employed an integrated computational approach combining network toxicology, machine learning, molecular docking, and molecular dynamics (MD) simulations to systematically explore the potential molecular mechanisms of AA-induced UTUC. We identified 97 shared potential targets of AAs and UTUC. Enrichment analyses revealed their significant involvement in lipid metabolism, xenobiotic detoxification, and cancer-related pathways such as PI3K-Akt signaling. Topological analysis of the protein-protein interaction network and a nested cross-validation machine learning model highlighted five core genes: CASP3, EGFR, PARP1, PTGS2, and HSP90AA1. Molecular docking predicted high binding affinities of AA with these core targets, particularly for PTGS2 (-9.3
Methyl-4-hydroxybenzoate induces osteoporosis via the AKT1/LC3B/Beclin1 autophagy signaling pathway: Integrati… MEDIUM▼
BACKGROUND: As public awareness of environmental issues grows and research on ecological pollutants advances, mounting evidence indicates that Methyl-4-hydroxybenzoate (MEP) is associated with the development of various diseases. This study aims to uncover the key genes and underlying molecular mechanisms by which MEP influences osteoporosis (OP). METHODS: This study integrates network toxicology, molecular docking, and molecular dynamics simulation approaches. Potential targets of the environmental contaminant were identified using the Comparative Toxicogenomics Database (CTD). In contrast, osteoporosis-related targets were retrieved from the Gene Expression Omnibus (GEO), GeneCards, and Online Mendelian Inheritance in Man (OMIM) databases. The intersection between MEP and OP targets was subsequently analyzed using PPI networks and functional enrichment analyses to identify core targets and pathways. For experimental validation, Sprague-Dawley rats were administered MEP via gavage for
Biomimetic cancer cell membrane-coated liposomal nanocarriers loaded with silibinin suppress gastric cancer pr…▼
Exploring synergistic therapeutic potential of Erlotinib and artemisinin in non-small cell lung Cancer (NSCLC)…▼
Desidustat's cardioprotective mechanisms in heart failure: a network pharmacology, molecular docking and dynam…▼
✗ Opposing Evidence 9
IL-25 (IL-17E) is a T-helper cell type 2 (Th2) cytokine best described as a potentiator of Th2 memory responses. Reports of expression of its receptor, IL-25R, on airways structural cells suggest a wider role for IL-25 in remodeling. We hypothesized that IL-25 stimulates local angiogenesis in the asthmatic bronchial mucosa. Immunoreactive IL-25(+), IL-25R(+), and CD31(+) (endothelial) cells in sections of bronchial biopsies from asthmatics and controls were detected by immunohistochemistry. The effect of IL-25 on angiogenesis was examined using an in vitro assay. Real-time PCR was used to detect expression of IL-25R and VEGF mRNA in cultured human vascular endothelial cells (HUVEC), and a cell proliferation kit (WST-8) was used to measure the effect of IL-25 on HUVEC proliferation. Immunostaining showed that IL-25(+), IL-25R(+), and CD31(+)/IL-25R(+) cells were significantly elevated in the bronchial mucosa of asthmatics compared with controls (P < 0.003). In asthmatics, the numbers of
Feinberg (2012) [8] suggests that science so far cannot "reduce critical features of consciousness to neural processes." But this poses an unrealistic standard. If science required full reductive explanations, neither Newton nor Darwin would be remembered today, since neither gave a reductive account of gravity or heredity. Indeed, we do not have such full reductions today. Useful theories, like Darwin's, are often not reductionistic to biological cells like neurons, though they can offer explanations of basic puzzles. Even theoretical physics cannot explain mountain avalanches and oak trees at the level of fundamental particles. Yet physics is a widely admired model of scientific theory. Judging by more modest historical standards we are making steady progress on Feinberg's four basic questions.
HSP90 inhibition with 17-AAG paradoxically reduces tau aggregation more effectively than HSP90 activation, sug… 0.79▼
β-lactam antibiotics inhibit bacterial cell wall assembly and, under classical microbiological culture conditions that are generally hypotonic, induce explosive cell death. Here, we show that under more physiological, osmoprotective conditions, for various Gram-positive bacteria, lysis is delayed or abolished, apparently because inhibition of class A penicillin-binding protein leads to a block in autolytic activity. Although these cells still then die by other mechanisms, exogenous lytic enzymes, such as lysozyme, can rescue viability by enabling the escape of cell wall-deficient "L-form" bacteria. This protective L-form conversion was also observed in macrophages and in an animal model, presumably due to the production of host lytic activities, including lysozyme. Our results demonstrate the potential for L-form switching in the host environment and highlight the unexpected effects of innate immune effectors, such as lysozyme, on antibiotic activity. Unlike previously described dorman
Chronic HSP90 overactivation leads to cellular stress and mitochondrial dysfunction in primary cortical neuron… 0.71▼
HSP90-mediated tau disaggregation shows limited efficacy against mature neurofibrillary tangles and may only a… 0.75▼
OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy associated with proteinuria detected by 24-hour urine collection (≥0.3 g/24 h) or protein/creatinine ratio (≥30 mg/mmol). The albumin/creatinine ratio (ACR) is used outside pregnancy to detect abnormal amounts of albumin in the urine, but there is little data on its value in pregnancy. Our objective was to determine the diagnostic threshold for ACR to detect significant proteinuria in women investigated for preeclampsia. METHODS: A prospective observational study involving 99 hypertensive women (≥140/90 mm Hg) over 20 weeks gestation who were hospitalized at 2 Canadian tertiary centres. A 24-hour urine collection and a morning urine sample were collected. The optimal ACR threshold was determined by a receiver operating characteristic (ROC) curve using the 24-hour collection as the reference test; sensitivity and specificity analyses were performed. Maternal and perinatal characteristics were extracted from medical records.
Investigating the clinical efficacy, safety and molecular mechanism of sulforaphane in autism spectrum disorde… MEDIUM▼
BACKGROUND: Sulforaphane, a natural antioxidant rich in cruciferous vegetables, has emerged as a promising dietary supplement for autism spectrum disorder (ASD). However, its therapeutic efficacy remains controversial, and the pharmacological mechanisms are not fully elucidated. METHODS: Eligible randomized controlled trials were retrieved from PubMed, Web of Science, Embase, and Cochrane Library databases. Review Manager 5.4 was used for meta-analysis and bias risk assessment. Network pharmacology, Mendelian randomization, GEO data analyses, molecular docking, and molecular dynamics simulation were employed to explore the mechanisms of sulforaphane in ASD. RESULTS: Six trials involving 333 participants were included in the meta-analysis. Pooled results demonstrated that both 4-5 weeks and 8-10 weeks of sulforaphane supplementation significantly decreased the scores on the Social Responsiveness Scale compared to placebo controls. No significant difference was observed in the incidence
The mechanism of probiotics in pregnancy outcomes in overweight or obese pregnant women based on meta-analysis… MEDIUM▼
BACKGROUND: The prevalence of obesity among women of reproductive age is increasing worldwide. Obesity significantly increases the risk of adverse pregnancy outcomes. The effectiveness of probiotics in improving the pregnancy outcomes of overweight or obese pregnant women is still controversial. METHODS: PubMed, Embase, Scopus, Cochrane, and Web of Science were searched for relevant articles up to May 30, 2025. Revman 5.4 was used for the meta-analysis. In network pharmacology, the gutMGene database was used to obtain the bioactive components of probiotics, and the SwissTargetPrediction platform was used to predict the targets of the active components. The related targets of diseases were obtained through OMIM and GeneCards databases and the bioactive compound-target network was constructed. AutoDockTools software was used for molecular docking verification. RESULTS: Eight randomized controlled trials (RCTs) involving 1563 participants were included in the meta-analysis.The results sho
Gigantol: a principal bioactive constituent of Dendrobium species-multi-target mechanisms, network pharmacolog… MEDIUM▼
ETHNOPHARMACOLOGICAL RELEVANCE: Gigantol, a naturally occurring bibenzyl compound isolated mainly from Dendrobium species, is traditionally used in Chinese and Southeast Asian medicine to nourish Yin, reduce internal heat, and treat inflammation-related diseases. Its broad pharmacological activities support its traditional applications and highlight its potential as a therapeutic agent. AIM OF THE STUDY: This review compiles existing evidence regarding the phytochemistry, pharmacological effects, pharmacokinetics, and molecular mechanisms of gigantol, while highlighting critical research gaps and future development directions. MATERIALS AND METHODS: An extensive literature search was conducted using the PubMed and China National Knowledge Infrastructure (CNKI) databases until June 2025. Data on gigantol extraction, pharmacological activities, in vitro and in vivo studies, molecular docking, network pharmacology, and pharmacokinetics were collected and analyzed. RESULTS: Gigantol exhibi
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Domain Expert Response: Translating Tau Spreading Hypotheses to Clinical Impact
Preamble: Where We Stand Today
The therapeutic landscape for Alzheimer's offers a sobering context: three amyloid-targeting antibodies have received accelerated/traditional approval since 2021, yet none have demonstrated robust cognitive preservation in isolation. This changes the calculus for tau-targeting strategies. The question is no longer whether to target tau, but where in the pathological cascade gives the best risk-benefit ratio for intervention. The hypotheses you've proposed sit at that
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Price History
| Event | Price | Change | Source | Time | |
|---|---|---|---|---|---|
| 📄 | New Evidence | $0.463 | ▲ 2.1% | evidence_batch_update | 2026-04-13 02:18 |
| 📄 | New Evidence | $0.453 | ▲ 2.5% | evidence_batch_update | 2026-04-13 02:18 |
| ⚖ | Recalibrated | $0.442 | ▲ 0.9% | 2026-04-12 18:34 | |
| ⚖ | Recalibrated | $0.438 | ▼ 0.3% | 2026-04-12 10:15 | |
| ⚖ | Recalibrated | $0.440 | ▼ 2.5% | 2026-04-12 05:13 | |
| ⚖ | Recalibrated | $0.451 | ▼ 0.9% | 2026-04-10 15:58 | |
| ⚖ | Recalibrated | $0.455 | ▲ 1.0% | 2026-04-10 15:53 | |
| ⚖ | Recalibrated | $0.450 | ▲ 0.8% | 2026-04-08 22:18 | |
| ⚖ | Recalibrated | $0.447 | ▼ 5.4% | 2026-04-08 18:39 | |
| ⚖ | Recalibrated | $0.472 | ▼ 2.6% | 2026-04-06 04:04 | |
| 📄 | New Evidence | $0.485 | ▲ 2.2% | evidence_batch_update | 2026-04-04 09:08 |
| ⚖ | Recalibrated | $0.475 | ▼ 4.1% | 2026-04-03 23:46 | |
| ⚖ | Recalibrated | $0.495 | ▼ 7.3% | 2026-04-02 21:55 | |
| ⚖ | Recalibrated | $0.534 | ▼ 2.5% | market_recalibrate | 2026-04-02 19:14 |
| 📄 | New Evidence | $0.548 | ▲ 0.8% | market_dynamics_seed | 2026-04-02 18:16 |
Clinical Trials (7) Relevance: 12%
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📚 Cited Papers (73)
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No DepMap CRISPR Chronos data found for HSP90AA1.
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Dependency Graph (7 upstream, 1 downstream)
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Knowledge Subgraph (126 edges)
Activate TREM2 signaling pathways to reprogram microglia from tau-propagating phenotype to tau-clear (1)
CHMP4B modulates tau propagation (1)
Deploy selective small molecule inhibitors targeting the tau-binding domain of LRP1 to prevent cellu (1)
Design allosteric modulators that specifically enhance HSP90's tau disaggregation activity without a (1)
Design selective allosteric activators of VCP/p97 ATPase activity specifically for tau-containing au (1)
Develop selective modulators of neurexin-neuroligin interactions to create synaptic barriers that pr (1)
HSP90AA1 modulates tau propagation (1)
LRP1 modulates tau propagation (1)
NLGN1 modulates tau propagation (1)
SNAP25 modulates tau propagation (1)
TREM2 modulates tau propagation (1)
Target ESCRT-III complex components (CHMP4B, VPS4) to selectively reduce tau-containing extracellula (1)
Target SNAP25 interactions to prevent tau uptake at presynaptic terminals during vesicle recycling. (1)
VCP modulates tau propagation (1)
associated with (7)
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regulates (15)
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therapeutic target (7)
Mechanism Pathway for HSP90AA1
Molecular pathway showing key causal relationships underlying this hypothesis
graph TD
HSP90AA1["HSP90AA1"] -->|regulates| HSP90_Tau_Disaggregation_["HSP90-Tau Disaggregation Complex Enhancement"]
HSP90AA1_1["HSP90AA1"] -->|regulates| Tau_Propagation["Tau Propagation"]
HSP90AA1_2["HSP90AA1"] -->|participates in| Tau_protein___microtubule["Tau protein / microtubule-associated pathway"]
HSP90AA1_3["HSP90AA1"] -->|associated with| Alzheimer_s_Disease["Alzheimer's Disease"]
HSP90AA1_4["HSP90AA1"] -->|Design allosteric| hsp90aa1_tau_interaction["hsp90aa1_tau_interaction"]
hsp90aa1_tau_interaction_5["hsp90aa1_tau_interaction"] -->|HSP90AA1 modulates| tau_propagation["tau_propagation"]
HSP90AA1_6["HSP90AA1"] -->|co associated with| VCP["VCP"]
HSP90AA1_7["HSP90AA1"] -->|co associated with| LRP1["LRP1"]
CHMP4B["CHMP4B"] -->|co associated with| HSP90AA1_8["HSP90AA1"]
HSP90AA1_9["HSP90AA1"] -->|co associated with| SNAP25["SNAP25"]
HSP90AA1_10["HSP90AA1"] -->|co associated with| TREM2["TREM2"]
HSP90AA1_11["HSP90AA1"] -->|co associated with| NLGN1["NLGN1"]
HSP90AA1_12["HSP90AA1"] -->|co associated with| HSP90["HSP90"]
style HSP90AA1 fill:#ce93d8,stroke:#333,color:#000
style HSP90_Tau_Disaggregation_ fill:#4fc3f7,stroke:#333,color:#000
style HSP90AA1_1 fill:#ce93d8,stroke:#333,color:#000
style Tau_Propagation fill:#4fc3f7,stroke:#333,color:#000
style HSP90AA1_2 fill:#ce93d8,stroke:#333,color:#000
style Tau_protein___microtubule fill:#81c784,stroke:#333,color:#000
style HSP90AA1_3 fill:#ce93d8,stroke:#333,color:#000
style Alzheimer_s_Disease fill:#ef5350,stroke:#333,color:#000
style HSP90AA1_4 fill:#ce93d8,stroke:#333,color:#000
style hsp90aa1_tau_interaction fill:#4fc3f7,stroke:#333,color:#000
style hsp90aa1_tau_interaction_5 fill:#4fc3f7,stroke:#333,color:#000
style tau_propagation fill:#81c784,stroke:#333,color:#000
style HSP90AA1_6 fill:#ce93d8,stroke:#333,color:#000
style VCP fill:#ce93d8,stroke:#333,color:#000
style HSP90AA1_7 fill:#ce93d8,stroke:#333,color:#000
style LRP1 fill:#ce93d8,stroke:#333,color:#000
style CHMP4B fill:#ce93d8,stroke:#333,color:#000
style HSP90AA1_8 fill:#ce93d8,stroke:#333,color:#000
style HSP90AA1_9 fill:#ce93d8,stroke:#333,color:#000
style SNAP25 fill:#ce93d8,stroke:#333,color:#000
style HSP90AA1_10 fill:#ce93d8,stroke:#333,color:#000
style TREM2 fill:#ce93d8,stroke:#333,color:#000
style HSP90AA1_11 fill:#ce93d8,stroke:#333,color:#000
style NLGN1 fill:#ce93d8,stroke:#333,color:#000
style HSP90AA1_12 fill:#ce93d8,stroke:#333,color:#000
style HSP90 fill:#ce93d8,stroke:#333,color:#000
3D Protein Structure
🧬 HSP90AA1 — PDB 2CG9 Click to expand 3D viewer
Source Analysis
Tau propagation mechanisms and therapeutic interception points
neurodegeneration | 2026-04-04 | completed
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