protein

HSP90

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about HSP90: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

622Connections

9Hypotheses

18Analyses

50Outgoing

50Incoming

10Experiments

20Debates

Summary

HSP90 is a protein involved in neurodegeneration research. Key relationships include: co discussed, protects against, activates. Associated with ALS, Inflammation, Neuroinflammation. Connected to 21 entities in the SciDEX knowledge graph.

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🔬 Protein Info

Gene Symbol	HSP90
Aliases	Heat Shock Protein 90
Protein Type	Chaperone
Function	is an important component in the neurobiology of neurodegenerative diseases.
Molecular Weight	90 kDa
Amino Acids	220 aa
Pathways	Apoptosis, Autophagy, Chaperone, Oxidative Stress
GeneCards	HSP90
Human Protein Atlas	HSP90
Associated Diseases	ALS, Alzheimer's disease, Depression, HUNTINGTON, HUNTINGTON'S
Known Drugs/Compounds	17-AAG
Interactions	AD, AGING, AKT, ALS, ALZHEIMER, ALZHEIMER'S DISEASE
KG Connections	615 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (12)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    HSP90["HSP90"]
    Neuroinflammation{"Neuroinflammation"}
    HSP90 -->|"protects against"| Neuroinflammation
    ALS{"ALS"}
    HSP90 -->|"activates"| ALS
    Inflammation{"Inflammation"}
    HSP90 -->|"protects against"| Inflammation
    SFRP1["SFRP1"]
    HSP90 -->|"interacts with"| SFRP1
    INFLAMMATION["INFLAMMATION"]
    HSP90 -->|"protects against"| INFLAMMATION
    AXON["AXON"]
    HSP90 -->|"activates"| AXON
    NEUROINFLAMMATION["NEUROINFLAMMATION"]
    HSP90 -->|"protects against"| NEUROINFLAMMATION
    Schwann_Cell["Schwann Cell"]
    HSP90 -->|"expressed in"| Schwann_Cell
    Macrophage["Macrophage"]
    HSP90 -->|"expressed in"| Macrophage
    MACROPHAGE["MACROPHAGE"]
    HSP90 -->|"co discussed"| MACROPHAGE
    MACROPHAGES["MACROPHAGES"]
    HSP90 -->|"co discussed"| MACROPHAGES
    HSP90 -->|"co discussed"| NEUROINFLAMMATION
    AND["AND"]
    AND -->|"regulates"| HSP90
    AXON -->|"activates"| HSP90
    INFLAMMATION -->|"protects against"| HSP90
    style HSP90 fill:#1a3a4a,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0

Outgoing (412)

Target	Relation	Type	Str
protein folding	mediates	process	0.95
proteostasis	regulates	process	0.95
protein aggregation	suppresses	process	0.90
Proteostasis	regulates	process	0.90
GPX4	interacts_with	protein	0.90
Neuroinflammation	activates	process	0.90
tau degradation	prevents	process	0.90
tau stability	stabilizes	process	0.90
SFRP1	binds	protein	0.90
GPX4	promotes	protein	0.85
Alzheimer'S Disease	implicated_in	disease	0.80
TRAP1	interacts_with	protein	0.80
Mitochondria	associated_with	entity	0.80
Cyclophilin-D	associated_with	protein	0.80
STING	inhibits	gene	0.70
NLRP3	regulates	gene	0.70
STAT3	activates	gene	0.70
TNF	regulates	gene	0.70
SLC6A4	regulates	gene	0.70
MMP9	targets	gene	0.70
SOD1	expressed_in	gene	0.70
TAU	expresses	gene	0.70
VEGF	targets	gene	0.70
P2RX7	expresses	gene	0.70
P2RX7	activates	gene	0.70
TAU	activates	gene	0.70
STAT3	targets	gene	0.70
NLRP3	expressed_in	gene	0.70
NFKB	expresses	gene	0.70
IGF1	activates	gene	0.70
MICROGLIA	activates	cell_type	0.70
TAU	interacts_with	gene	0.70
MICROGLIA	expresses	cell_type	0.70
SOD2	activates	gene	0.70
SOD1	activates	gene	0.70
UNFOLDED PROTEIN RESPONSE	inhibits	pathway	0.70
RAGE	inhibits	gene	0.70
NEURONS	activates	cell_type	0.70
SQSTM1	activates	gene	0.70
Cancer	implicated_in	disease	0.70
PPID	regulates	protein	0.70
tau	protects	protein	0.70
protein aggregation compensation	modulates	mechanism	0.70
protein folding	modulates	process	0.70
PROTEIN_AGGREGATION	regulates	phenotype	0.70
proteostasis network	regulates	process	0.70
Cyclophilin-D	regulates	protein	0.70
tau client recognition	regulates	phenotype	0.70
neurodegeneration	activates	disease	0.65
Inflammation	inhibits	disease	0.65

Incoming (210)

Source	Relation	Type	Str
Tim-AIII	binds_to	drug	0.95
PER2	binds_to	protein	0.92
SFRP1	binds	protein	0.90
17-AAG	inhibits	drug	0.80
APE2	binds	gene	0.80
FKBP5	co_chaperone	gene	0.80
AMPK	expresses	gene	0.70
AMPK	inhibits	gene	0.70
BECN1	activates	gene	0.70
CAT	targets	gene	0.70
APP	expressed_in	gene	0.70
DRD2	targets	gene	0.70
hdac6	regulates	protein	0.70
PYROPTOSIS	regulates	phenotype	0.65
BCL2	targets	gene	0.65
AMPK	activates	gene	0.65
HSP27	expressed_in	gene	0.60
APP	associated_with	gene	0.60
CNR1	associated_with	gene	0.60
ATF4	inhibits	gene	0.60
BECLIN1	inhibits	gene	0.60
GPX4	protects_against	gene	0.60
LYSOSOME	inhibits	gene	0.60
AUTOPHAGY	inhibits	gene	0.60
TNF-Α	inhibits	gene	0.60
AGING	activates	gene	0.60
PARKINSON	activates	gene	0.60
ALZHEIMER'S DISEASE	activates	gene	0.60
GPX4	expresses	gene	0.60
AMYOTROPHIC LATERAL SCLEROSIS	regulates	disease	0.60
AKT	regulates	gene	0.60
CDK5	activates	gene	0.60
CDK5	inhibits	gene	0.60
FRONTOTEMPORAL DEMENTIA	disrupts	disease	0.60
FTD	disrupts	disease	0.60
HMGB1	regulates	gene	0.60
FERROPTOSIS	activates	pathway	0.60
APOPTOSIS	inhibits	pathway	0.60
BAX	inhibits	gene	0.60
APOE	activates	gene	0.60
HMGB1	co_discussed	gene	0.60
GPX4	therapeutic_target	gene	0.60
ATG13	inhibits	gene	0.60
POLE	activates	gene	0.60
UBIQUITIN	regulates	gene	0.60
ASC	expressed_in	gene	0.60
HSP60	expressed_in	gene	0.60
HDAC6	activates	gene	0.60
HDAC6	cleaves	gene	0.60
HSP70	interacts_with	gene	0.60

Targeting Hypotheses (9)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
HSP90-Tau Disaggregation Complex Enhancement	0.634	neurodegeneration	Tau propagation mechanisms and therapeut
HSP90-Tau Disaggregation Complex Enhancement	0.575	Alzheimer's Disease	Tau propagation mechanisms and therapeut
Aggregation-prone sequences trigger HSP90-dependent conforma	0.497	protein biochemistry	Do chaperones selectively recognize path
Membrane-Localized HSP90 Disruption	0.455	drug discovery	What are the minimal structural requirem
Allosteric Pocket Exploitation for Tau-Specific HSP90 Modula	0.455	drug discovery	What are the minimal structural requirem

Amyloidogenic segments undergo conformational templating by	0.380	protein biochemistry	Do chaperones selectively recognize path
HSP90-CDC37 complex recognizes exposed hydrophobic clusters	0.380	protein biochemistry	Do chaperones selectively recognize path
CK2-mediated HSP90α phosphorylation switches client discrimi	0.363	protein biochemistry	Do chaperones selectively recognize path
HSP90-cochaperone complexes preferentially stabilize interme	0.000	protein biochemistry	Do chaperones selectively recognize path

Mentioning Analyses (18)

Scientific analyses that reference this entity

Should microtubule-stabilizing drugs be reconsidered as therapeutic targets for

neurodegeneration | 2026-04-15 | 2 hypotheses Top: 0.634

What is the atomic-resolution structure of K280-acetylated tau and how does it t

structural biology | 2026-04-13 | 1 hypotheses Top: 0.643

What is the therapeutic window between insufficient and toxic levels of TDP-43 a

neurodegeneration | 2026-04-12 | 2 hypotheses Top: 0.895

Why have numerous phase 3 clinical trials failed despite advances in understandi

neurodegeneration | 2026-04-12 | 1 hypotheses Top: 0.566

Does DNAJB6 directly inhibit cross-seeding between tau, α-synuclein, and TDP-43

neurodegeneration | 2026-04-12 | 0 hypotheses

Experiments (10)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Endothelial CD2AP knockdown effects on memory in male mice	validation	Alzheimer's disease	0.900	male mice	proposed	N/A
Amyloid plaque load analysis in triple-mutant mouse brains	exploratory	Alzheimer's disease	0.880	APP/PSEN1/GD3S-/- triple-trans	proposed	N/A
Reelin treatment rescue via ApoER2 in CD2AP mutant mice	validation	Alzheimer's disease	0.870	mice	proposed	N/A
MRI Phenotyping Method Concordance in Serbian AD Cohort	clinical	Alzheimer's disease	0.850	human patients	proposed	N/A
Endothelin-1 receptor A antagonist rescue in male CD2AP mice	validation	Alzheimer's disease	0.850	male mice	proposed	N/A
Endothelin-1 receptor A antagonist rescue experiment	validation	Alzheimer's disease	0.850	mice	proposed	N/A
In vivo BBB transport of LPS-carrying bEVs	validation	Alzheimer's disease	0.850	mice	proposed	N/A
Neuroimmune modulation and Aβ clearance mechanisms	exploratory	Alzheimer's disease	0.820	Microglia and astrocytes	proposed	N/A
16S rRNA sequencing of gut microbiome in PH-PS treated mice	exploratory	Alzheimer's disease	0.800	5×FAD transgenic mice	proposed	N/A
Competing endogenous RNA (ceRNA) network construction	exploratory	Alzheimer's disease	0.750	computational network analysis	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Gigantol: a principal bioactive constituent of Dendrobium species-multi-target m [PMID:40939944]	Shi S, Zhu C, Xu J, Sui Q, Zhu S, Zhang	Journal of ethnopharmacology	2026
Biomimetic cancer cell membrane-coated liposomal nanocarriers loaded with silibi [PMID:41585438]	Yao J, Sun Q, Zhang X, Yang D, Wu H et a	Mater Today Bio	2026
Exploring synergistic therapeutic potential of Erlotinib and artemisinin in non- [PMID:41672289]	Suleman F, Khan T, Alshehade SA, Ali M,	Clin Chim Acta	2026
Methyl-4-hydroxybenzoate induces osteoporosis via the AKT1/LC3B/Beclin1 autophag [PMID:41740552]	Fu F, Wang W, Li Y, Shi S, Huang J, Liu	Ecotoxicology and environmenta	2026
Chronic Thermal Stress During Early Zebrafish (Danio rerio) Development Induces [PMID:41793424]	Adzijovski M, Schultz AG, Oxley APA, Ber	Fish physiology and biochemist	2026
α-Glucosidase inhibitor: identifying key targets and mechanisms in type 2 diabet [PMID:41907120]	Garg SS, Vijh D, Gupta P, Gupta J, Malik	3 Biotech	2026
Elucidating the mechanisms of aristolochic acid-induced upper tract urothelial c [PMID:41780445]	Liu T, Yao Y, Xu Y, Zhang H, Sun L, Zhan	Computational biology and chem	2026
A Study on the Mechanism of Acetyl Tributyl Citrate-Induced Infertility Toxicity [PMID:41898778]	Sun X, Chen P, Han Y, Du Y, Sun S, Miu J	International journal of molec	2026
Investigating the clinical efficacy, safety and molecular mechanism of sulforaph [PMID:41275316]	Long J, Liao X, Tang Z, Han K, Chen J, W	BMC pharmacology & toxicology	2025
Cerebrospinal fluid HSP90AA1, HSPA4, and STUB1/CHIP levels in Alzheimer's diseas [PMID:40116694]	Sordu P, Alaylıoğlu M, Samancı B, Bulu E	J Alzheimers Dis	2025
The chaperones HSP90AA1, HSP90AB1 and BAG3 are specifically distributed among hu [PMID:40436281]	Soriano-Herrador C, Ubeda-Banon I, Villa	Neurobiol Dis	2025
Mapping the pathogenic nexus: Gene overlap and protein interaction networks in A [PMID:40973403]	Chowdhury MR, Deepa VS, Raja VK	Adv Protein Chem Struct Biol	2025
The mechanism of probiotics in pregnancy outcomes in overweight or obese pregnan [PMID:40859213]	Zhong T, Sun J, Miao M, Sun G	BMC pregnancy and childbirth	2025
Chrysotoxine regulates ferroptosis and the PI3K/AKT/mTOR pathway to prevent cerv [PMID:39557107]	Zhou J, Guo Z, Peng X, Wu B, Meng Q, Lu	Journal of ethnopharmacology	2025
A novel MTORC2-AKT-ROS axis triggers mitofission and mitophagy-associated execut [PMID:38261660]	Iskandar K, Foo J, Liew AQX, Zhu H, Rama	Autophagy	2024
Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal [PMID:38247340]	Astillero-Lopez V, Villar-Conde S, Gonza	Brain pathology (Zurich, Switz	2024
Efficient analysis of toxicity and mechanisms of environmental pollutants with n [PMID:37858827]	Huang S	The Science of the total envir	2023
Regulation of TFEB nuclear localization by HSP90AA1 promotes autophagy and longe [PMID:35941759]	Yang S, Nie T, She H, Tao K, Lu F et al.	Autophagy	2023
Network pharmacology and molecular docking combined with widely targeted metabol [PMID:37150086]	Liu Y, Sun W, Shen N, Hao W, Xin H, Che	Computers in biology and medic	2023
Paeoniflorin protects against cisplatin-induced acute kidney injury through targ [PMID:36972781]	Zhang MY, Ma LJ, Jiang L, Gao L, Wang X,	Journal of ethnopharmacology	2023

Debates (20)

Multi-agent debates referencing this entity

While the study demonstrates TDP-43 triggers mPTP-mediated mtDNA release, the mo

closed · Rounds: 4 · Score: 0.77 · 2026-04-21

The debate revealed fundamental uncertainty about whether HSP70/HSP90 systems ca

closed · Rounds: 4 · Score: 0.73 · 2026-04-21

The debate hinged on whether HSP90 adopts unique conformations when bound to tau

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

The debate highlighted fundamental disagreement about tau's role - whether aggre

closed · Rounds: 4 · Score: 1.00 · 2026-04-20

The debate revealed that DNAJB6 evidence is limited to polyglutamine aggregation

closed · Rounds: 4 · Score: 0.79 · 2026-04-16

The abstract challenges the rationale for using microtubule-stabilizing drugs in

closed · Rounds: 4 · Score: 0.68 · 2026-04-15

The debate proposed K280 acetylation creates a β-sheet nucleation interface but

closed · Rounds: 4 · Score: 0.86 · 2026-04-14

The debate proposed K280 acetylation creates a β-sheet nucleation interface but

closed · Rounds: 4 · Score: 0.74 · 2026-04-14

The debate highlighted a critical dosing paradox where both hypo- and hypermethy

closed · Rounds: 4 · Score: 0.82 · 2026-04-12

Why have numerous phase 3 clinical trials failed despite advances in understandi

closed · Rounds: 5 · Score: 0.67 · 2026-04-12

Related Research

Hypotheses and analyses mentioning HSP90 in their description or question text

HSP90

Understanding Entity Pages

Summary

Wiki Pages (12)

HSP90 Protein (Heat Shock Protein 90)

HSP90AB1 Gene

Alzheimer's Disease HSP70/HSP90 Chaperone and Protein Folding Therapy Companies

HSP90 Co-chaperone CDC37 Modulation

HSP90 Inhibitors for Neurodegeneration

HSP90AA1 Gene

HSP70/HSP90 Modulators

HSP90B1 Gene

HSP90B1 — Heat Shock Protein 90 Beta Family Member 1

HSP90AA1 Protein

HSP90AB1 Protein

HSP90 — Heat Shock Protein 90

Pathway Diagram

Outgoing (412)

Incoming (210)

Targeting Hypotheses (9)

Mentioning Analyses (18)

Should microtubule-stabilizing drugs be reconsidered as therapeutic targets for

What is the atomic-resolution structure of K280-acetylated tau and how does it t

What is the therapeutic window between insufficient and toxic levels of TDP-43 a

Why have numerous phase 3 clinical trials failed despite advances in understandi

Does DNAJB6 directly inhibit cross-seeding between tau, α-synuclein, and TDP-43

Do tau aggregates represent protective responses or primary pathogenic drivers i

Do tau-specific HSP90 conformational states exist that differ from other client

Do chaperones selectively recognize pathological vs physiological protein confor

What are the minimal structural requirements for HSP70/HSP90 inhibitors to achie

How do host cell factors influence the conformation and propagation properties o

What upstream mechanisms cause TDP-43 to trigger mPTP opening and can this be th

What molecular mechanisms drive tissue-specific phenotypes in Mendelian neurolog

Tau propagation mechanisms and therapeutic interception points

Digital biomarkers and AI-driven early detection of neurodegeneration

APOE4 structural biology and therapeutic targeting strategies

Mechanistic role of APOE in neurodegeneration

TDP-43 phase separation therapeutics for ALS-FTD

APOE4 structural biology and therapeutic targeting strategies

Experiments (10)

Related Papers (20)

Debates (20)

While the study demonstrates TDP-43 triggers mPTP-mediated mtDNA release, the mo

The debate revealed fundamental uncertainty about whether HSP70/HSP90 systems ca

The debate hinged on whether HSP90 adopts unique conformations when bound to tau

The debate highlighted fundamental disagreement about tau's role - whether aggre

The debate revealed that DNAJB6 evidence is limited to polyglutamine aggregation

The abstract challenges the rationale for using microtubule-stabilizing drugs in

The debate proposed K280 acetylation creates a β-sheet nucleation interface but

The debate proposed K280 acetylation creates a β-sheet nucleation interface but

The debate highlighted a critical dosing paradox where both hypo- and hypermethy

Why have numerous phase 3 clinical trials failed despite advances in understandi

Related Research

Amyloidogenic segments undergo conformational templating by HSP90-HSP70 heteroco

HSP90-CDC37 complex recognizes exposed hydrophobic clusters as amyloidogenic dan

CK2-mediated HSP90α phosphorylation switches client discrimination toward diseas

HSP90-cochaperone complexes preferentially stabilize intermediate misfolded stat