entity

UPR

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about UPR: 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.

7Connections
16Hypotheses
1Analyses
3Outgoing
4Incoming
17Experiments
1Debates

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Wiki Pages (7)

Knowledge base pages for this entity

Canonical Page

ER Stress and Unfolded Protein Response in Corticobasal Degeneration

mechanism · 1780 words

Unfolded Protein Response (UPR)

mechanism · 3651 words

ER Stress & UPR Therapeutics Investment Landscape

investment · 2220 words

ER Stress and UPR Disease Comparison

mechanism · 2087 words

Unfolded Protein Response (UPR) Neurons

cell · 1998 words

ER Stress and UPR Modulator Therapy for Neurodegeneration

therapeutic · 1403 words

Outgoing (3)

TargetRelationTypeStr
PROTEIN_FOLDINGactivatesphenotype0.72
SYNAPTIC_FUNCTIONregulatesphenotype0.56
APOPTOSISactivatesphenotype0.56

Incoming (4)

SourceRelationTypeStr
ER_STRESSactivatesphenotype0.72
ER STRESSactivatesentity0.70
DAP12involved_ingene0.60
RAPAMYCINassociated_withdrug0.45

Targeting Hypotheses (16)

Hypotheses where this entity is a therapeutic target

HypothesisScoreDiseaseAnalysis
SIRT1 Activation Couples Mitochondrial Biogenesis to Ferropt 0.824 neurodegeneration View
Cell-Type Specific TREM2 Upregulation in DAM Microglia 0.761 Alzheimer's Disease SEA-AD Gene Expression Profiling — Allen
Endothelial Glycocalyx Regeneration via Syndecan-1 Upregulat 0.705 neurodegeneration Perivascular spaces and glymphatic clear
TFEB-mediated transcriptional upregulation of lysosomal gene 0.680 neuroscience Lysosomal dysfunction and cathepsin leak
TNF-α/NF-κB Axis Upregulates P2RY12 in VSMCs 0.650 neurodegeneration What determines P2RY12 receptor expressi
Neuronal TET1 Upregulation Reactivates Immediate-Early Genes 0.640 neurodegeneration epigenetic reprogramming aging neurons
C1Q-Induced Foam Cell Formation via Scavenger Receptor Upreg 0.620 neuroinflammation What are the specific molecular mechanis
PDGF-BB/PDGFRβ/STAT3 Paracrine Signaling Axis Mediates Aβ-In 0.618 neurodegeneration How do perivascular cells specifically r
Age-Accelerated miR-155 Upregulation Primes Nigral Microglia 0.610 neuroinflammation How do regional, age, and sex-dependent
Astrocytic Connexin-43 Upregulation Enhances Neuroprotective 0.559 neurodegeneration Mitochondrial transfer between neurons a
EP4 Receptor Agonism for SLC7A11 Upregulation 0.550 neurodegeneration Can ferroptosis inhibitors prevent BBB d
TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1 0.496 neurodegeneration How do perivascular cells specifically r
Platelet-Derived PDGF-BB Primes VSMCs for P2RY12 Upregulatio 0.480 neurodegeneration What determines P2RY12 receptor expressi
HBOT at 1.5 ATA for 90 days restores BBB integrity by upregu 0.460 neurodegeneration What are the optimal oxygen pressure, du
Restoration of Neuronal Ketone Body Utilization via MCT1 Upr 0.450 metabolomics Metabolomic signatures of neurodegenerat
RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upre 0.442 neurodegeneration How do perivascular cells specifically r

Mentioning Analyses (1)

Scientific analyses that reference this entity

SEA-AD Single-Cell Analysis: Cell-Type Vulnerability in Alzheimer's Disease

neurodegeneration | 2026-04-04 | 5 hypotheses Top: 0.640

Experiments (17)

Experimental studies targeting or related to this entity

ExperimentTypeDiseaseScoreFeasibilityModelStatusEst. Cost
Anti-ASC antibody intracerebroventricular injection in APP/PS1 mice validation Alzheimer's disease 0.950 0.00 APP/PS1 transgenic mice (8 mon proposed N/A
Curcumin-Licorice Combination in D-galactose/Sodium Nitrite AD Model validation Alzheimer's disease 0.950 0.00 C57BL/6 mice proposed N/A
Irisin effects on osteogenic differentiation in mesenchymal stem cells exploratory bone fracture 0.900 0.00 mouse bone mesenchymal stem ce proposed N/A
SPP1 upregulation in perivascular cells in AD mouse models exploratory Alzheimer's disease 0.900 0.00 AD mouse models proposed N/A
Tet2 modulation in Aβ42-injured mouse hippocampal neurons exploratory Alzheimer's disease 0.900 0.00 primary mouse hippocampal neur proposed N/A
AAV-mediated Tet2 modulation in 2×Tg-AD mice behavioral study validation Alzheimer's disease 0.900 0.00 young APPswe/PSEN1 double-tran proposed N/A
Cerebrovascular function analysis in CD2AP mutant mice validation Alzheimer's disease 0.900 0.00 mice proposed N/A
Cx43 knockdown effects on mitochondrial transfer exploratory osteoarthritis 0.900 0.00 human bone marrow-derived MSCs proposed N/A
Cerebral blood flow regulation in CD2AP mutant mice validation Alzheimer's disease 0.880 0.00 mice proposed N/A
Abeta-induced cell death and aggregation in GD3S-deficient neurons exploratory Alzheimer's disease 0.850 0.00 primary neurons and astrocytes proposed N/A
Generation of Aβ-specific Tregs using CRISPR-Cas9 exploratory Alzheimer's disease 0.850 0.00 engineered Tregs proposed N/A
Confocal imaging of MSC-chondrocyte interactions during mitochondrial exploratory osteoarthritis 0.850 0.00 human bone marrow-derived MSCs proposed N/A
Cell-cell interaction analysis of perivascular-microglial crosstalk exploratory Alzheimer's disease 0.800 0.00 AD mouse models proposed N/A
Proposed experiment from debate on Perivascular spaces and glymphatic falsification Neurodegeneration 0.400 0.50 cell_line proposed $100,000
Blood-Brain Barrier Aging and Neurodegeneration — From Leakage to Neur validation Neurodegeneration 0.400 0.50 cell_line proposed $130,000
Vascular Contribution to Alzheimer's Disease — Beyond Amyloid validation Alzheimer's Disease 0.400 0.50 human proposed $2,280,000
Vascular Contributions to Alzheimer Disease and Mixed Pathology clinical Alzheimer's Disease 0.400 0.50 human proposed $5,460,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMIDAuthorsJournalYearCitations
Transcriptomic cytoarchitecture reveals principles of human neocortex organizati [PMID:37824655] Jorstad NL, Close J, Johansen N, Yanny A Science 2023 186
Integrated multimodal cell atlas of Alzheimer’s disease [PMID:37292694] Gabitto MI, Travaglini KJ, Rachleff VM, Research Square 2023 63
NETs induce ferroptosis of endothelial cells in LPS-ALI through SDC-1/HS and dow [PMID:38677244] Fei Y, Huang X, Ning F, Qian T, Cui J, W Biomed Pharmacother 2024 1
NAD(+) rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis. [PMID:37683629] Zhan R, Meng X, Tian D, Xu J, Cui H, Yan Neuron 2023 1
Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induce [PMID:34217286] Wang XY, Li XY, Wu CH, Hao Y, Fu PH, Mei Respir Res 2021 1
Astrocyte Networks as Therapeutic Targets in Glaucomatous Neurodegeneration. [PMID:34199470] Boal AM, Risner ML, Cooper ML, Wareham L Cells 2021 1
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797] Zhou Y, Song WM, Andhey PS, Swain A, Lev Nat Med 2020 1
The glycocalyx: a novel diagnostic and therapeutic target in sepsis. [PMID:30654825] Uchimido R, Schmidt EP, Shapiro NI Crit Care 2019 1
Moderate Effects of the Arginine to Histidine R47H Variant of the Triggering Rec [PMID:41890852] ["Ramirez G", "Hernandez D", "Teal A", " Research square 2026 0
Connexin43 Deficiency Leads to Ventricular Arrhythmias by Reprogramming Proline [PMID:41618855] ["Ying H", "Fan H", "Wang Y", "Jiang R", Advanced science (Weinheim, Ba 2026 0
Prenatal lipopolysaccharide exposure programs cardiac fibrosis via dysregulating [PMID:41789580] Wen Y, Yuan Y, Zhang H, Liu Y Molecular medicine reports 2026 0
Increased plasma soluble TREM2 levels in non-Alzheimer's dementia. [PMID:41920402] Güven Gamze; Gezegen Haşim; & Acta neurologica Belgica 2026 0
Pathogenic Significance of Serum Syndecan-1 and Syndecan-4 in Psoriasis. [PMID:41839009] Yıldırım MA, Korkmaz S, Çelik HHA, Büyük Cutis 2026 0
AI-guided design of cyclic peptide binders targeting TREM2 using CycleRFdiffusio [PMID:41435973] Cho S, Zhu R, Kuncewicz K, Duan H, Gabr Bioorg Med Chem Lett 2026 0
Astrocytes Protect Brain Metastatic Breast Cancer Cells From Chemotherapy Throug [PMID:41486609] Yakati V, Rao SS Biotechnol Bioeng 2026 0
ITAM-Syk signaling mediates the rebound phenomenon after anti-RANKL antibody dis [PMID:41490759] Ishizu H, Hasegawa T, Shimizu T, Yamamot Bone 2026 0
Oxaliplatin-artesunate conjugate intensifies suppression on colorectal cancer by [PMID:41520444] Tan Y, Yang T, Jiang S, Li S, Cai L et a J Inorg Biochem 2026 0
Loss of Triggering Receptor Expressed on Myeloid Cells 2 Impairs Microglial Func [PMID:41643896] Chen G, Wang Z, Zhao C, Wang C, Li Y et Am J Pathol 2026 0
Microglial metabolic reprogramming in Alzheimer's disease: Pathways, mechanisms, [PMID:41651180] Yang FG, Yang H, Han SW, Wang JT, Gao W Ageing Res Rev 2026 0
Plant-derived bioactive compounds modulate the gut microbiota in Alzheimer's dis [PMID:41678917] Xue D, Hu X, Li R, Sun T, Qian S et al. Phytomedicine 2026 0

Debates (1)

Multi-agent debates referencing this entity

SEA-AD Single-Cell Analysis: Cell-Type Vulnerability in Alzheimer's Disease

closed · Rounds: 4 · Score: 0.88 · 2026-04-04

Related Research

Hypotheses and analyses mentioning UPR in their description or question text

Neuronal TET1 Upregulation Reactivates Immediate-Early Genes and Restores Dendri

Score: 0.640 · neurodegeneration · 2026-04-22

**Molecular Mechanism and Rationale** The hypothesis centers on the ten-eleven translocation 1 (TET1) enzyme's critical

C1Q-Induced Foam Cell Formation via Scavenger Receptor Upregulation

Score: 0.620 · neuroinflammation · 2026-04-21

## Mechanistic Overview C1Q-Induced Foam Cell Formation via Scavenger Receptor Upregulation starts from the claim that m

PDGF-BB/PDGFRβ/STAT3 Paracrine Signaling Axis Mediates Aβ-Induced SPP1 Upregulat

Score: 0.618 · neurodegeneration · 2026-04-22

**Molecular Mechanism and Rationale** The proposed PDGF-BB/PDGFRβ/STAT3 signaling axis represents a complex intercellul

Age-Accelerated miR-155 Upregulation Primes Nigral Microglia for Parkinson's Dis

Score: 0.610 · neuroinflammation · 2026-04-22

## Mechanistic Overview Age-Accelerated miR-155 Upregulation Primes Nigral Microglia for Parkinson's Disease Pathology s

Astrocytic Connexin-43 Upregulation Enhances Neuroprotective Mitochondrial Donat

Score: 0.559 · neurodegeneration · 2026-04-02

Pharmacological enhancement of connexin-43 expression in astrocytes increases tunneling nanotube formation and mitochond

EP4 Receptor Agonism for SLC7A11 Upregulation

Score: 0.550 · neurodegeneration · 2026-04-25

PGE₂ signaling through EP4 receptor transcriptionally upregulates SLC7A11, enhancing cystine uptake and GSH synthesis to

TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1 Upregulation Through

Score: 0.496 · neurodegeneration · 2026-04-22

## Mechanistic Overview TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1 Upregulation Through CSF1R-Mediated

Platelet-Derived PDGF-BB Primes VSMCs for P2RY12 Upregulation

Score: 0.480 · neurodegeneration · 2026-04-21

## Mechanistic Overview Platelet-Derived PDGF-BB Primes VSMCs for P2RY12 Upregulation starts from the claim that modulat

HBOT at 1.5 ATA for 90 days restores BBB integrity by upregulating claudin-5 and

Score: 0.460 · neurodegeneration · 2026-04-25

HBOT promotes pericyte survival via PDGF-BB/PDGFR-β signaling and upregulates claudin-5 transcription through HIF-2α to

Restoration of Neuronal Ketone Body Utilization via MCT1 Upregulation

Score: 0.450 · metabolomics · 2026-04-25

Restoration of Neuronal Ketone Body Utilization via MCT1 Upregulation

RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upregulation in Perivasc

Score: 0.442 · neurodegeneration · 2026-04-22

## Mechanistic Overview RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upregulation in Perivascular Fibroblasts