concept

SASP

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about SASP: 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.

38Connections

20Hypotheses

4Analyses

19Outgoing

19Incoming

20Experiments

6Debates

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💡 Concept Info

Name	SASP
Key Genes/Proteins	NFKB, NFKB1, NF-κB
Related Diseases	Alzheimer's Disease, Alzheimer'S Disease, Aβ-induced neurotoxicity, fibrosis
Related Pathways	MAPK
Linked Hypotheses	25 hypotheses

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

Cellular Senescence Therapeutic Targeting

mechanism · 2429 words

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SASP (Senescence-Associated Secretory Phenotype) in Neurodegeneration

mechanism · 1407 words

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Pathway Diagram

graph TD
    SASP["SASP"]
    SASP -->|"expressed in"| Senescent_Microglia["Senescent Microglia"]
    SASP -->|"contributes to"| Neuroinflammation["Neuroinflammation"]
    SASP -->|"mediates"| chronic_inflammation["chronic inflammation"]
    SASP -->|"promotes"| tissue_dysfunction["tissue dysfunction"]
    SASP -->|"contributes to"| Alzheimer_s_Disease["Alzheimer's Disease"]
    SASP -.biomarker for.-> Cellular_Senescence["Cellular Senescence"]
    NF__B["NF-kappaB"] -->|"activates"| SASP
    NFKB["NFKB"] -->|"regulates"| SASP
    senescence["senescence"] -->|"causes"| SASP
    senescent_cells["senescent cells"] -->|"develops"| SASP
    NFKB1["NFKB1"] -->|"promotes"| SASP
    Senescent_Microglia -->|"expressed in"| SASP
    senomorphics["senomorphics"] -->|"inhibits"| SASP

Outgoing (19)

Target	Relation	Type	Str
Senescent Microglia	associated_with	cell_type	0.95
Senescent Microglia	expressed_in	cell_type	0.95
Neuroinflammation	associated_with	process	0.90
tissue dysfunction	promotes	process	0.90
Neuroinflammation	causes	process	0.90
chronic inflammation	mediates	process	0.90
chronic inflammation	promotes	process	0.90
neuroinflammation	promotes	process	0.90
Aβ-induced neurotoxicity	promotes	phenotype	0.90
tau-induced neurotoxicity	promotes	phenotype	0.90
MICROGLIA	interacts_with	cell_type	0.85
Neurodegeneration	promotes	process	0.85
Alzheimer's Disease	contributes_to	disease	0.85
Cellular Senescence	biomarker_for	process	0.85
SENESCENCE	associated_with	entity	0.80
Alzheimer'S Disease	contributes_to	disease	0.80
neuroinflammation	activates	pathway	0.80
neuroinflammation	induces	process	0.80
fibrosis	activates	disease	0.70

Incoming (19)

Source	Relation	Type	Str
senescent cells	develops	cell_type	0.95
senescence	causes	process	0.95
NFKB	activates	protein	0.95
Senescent Microglia	associated_with	cell_type	0.95
NF-κB	activates	protein	0.95
NFKB	regulates	entity	0.95
NFKB1	promotes	protein	0.95
Senescent Microglia	expressed_in	cell_type	0.90
senescent glial cells	mediates	cell_type	0.90
senomorphics	inhibits	drug	0.90
SDA-2026-04-01-gap-013	investigates	analysis	0.90
Cys-D	suppresses	drug	0.85
TGM2	drives	gene	0.85
NF-ΚB	regulates	pathway	0.80
MICROGLIA	promotes	cell_type	0.80
Tgm2	upregulates	gene	0.80
NF-κB	promotes	pathway	0.80
MAPK	causes	pathway	0.64
NLRP3	co_associated_with	gene	0.30

Targeting Hypotheses (20)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
SASP Modulation Rather Than Cell Elimination	0.981	-	Senescent cell clearance as neurodegener
SASP-Mediated Complement Cascade Amplification	0.910	neurodegeneration	Senolytic therapy for age-related neurod
Microglial Senescence Prevention via TREM2/SASP Axis	0.847	neurodegeneration	View
SASP-Driven Microglial Metabolic Reprogramming in Synaptic P	0.796	neurodegeneration	Senolytic therapy for age-related neurod
Targeting SASP-Complement Amplification Through HIF-1α Downs	0.793	neurodegeneration	What molecular mechanism causes VCP muta

SASP-Driven Aquaporin-4 Dysregulation	0.782	neurodegeneration	Senolytic therapy for age-related neurod
TBK1 Loss Locks Microglia in an Aged/Senescent Transcription	0.776	ALS	What are the mechanisms by which microgl
SASP-Mediated Cholinergic Synapse Disruption	0.763	neurodegeneration	Senolytic therapy for age-related neurod
Complement-SASP Amplification Cascade as Mechanistic Link	0.741	neurodegeneration	Why have anti-Aβ clinical trials failed
SASP Secretome-based Molecular Distinction via CXCL1/CXCL2/M	0.720	neurodegeneration	How can senescent microglia be molecular
SASP-Secreted MMP-9 from Senescent Microglia Generates Patho	0.682	ALS	What are the mechanisms by which microgl
TNF-α/IL-1β-Cx43 Hemichannel Axis as Upstream Link Between S	0.663	cell biology	What is the relative contribution of con
SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs	0.652	neurodegeneration	What are the specific PTM changes in syn
NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Compl	0.592	neurodegeneration	test
NLRP3 Inflammasome Blockade as Upstream Intervention to Prev	0.566	neurodegeneration	Why have numerous phase 3 clinical trial
Timed Senolytic Therapy Eliminates p16^Ink4a/p21^Cip1-Senesc	0.564	neuroinflammation	What molecular mechanisms drive the tran
H2: SASP Neutralization via JAK/STAT Inhibition Preserves As	0.550	neurodegeneration	Do APOE4-driven senescent astrocytes cau
Combined NAMPT-Alectinib Targeting of SASP-Complement Cascad	0.549	neuroinflammation	How does Alectinib, a kinase inhibitor,
NFκB/C1Q SASP Modulation for Synaptic Protection	0.534	neurodegeneration	View
P2RY12 activation induces cellular senescence in cerebral VS	0.373	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio

Mentioning Analyses (4)

Scientific analyses that reference this entity

What are the mechanisms by which microglial senescence contributes to ALS pathol

neurodegeneration | 2026-04-26 | 4 hypotheses Top: 0.776

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

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

Senescent cell clearance as neurodegeneration therapy

neurodegeneration | 2026-04-04 | 7 hypotheses Top: 1.000

Senolytic therapy for age-related neurodegeneration

neurodegeneration | 2026-04-01 | 8 hypotheses Top: 0.910

Experiments (20)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Single-cell RNA sequencing analysis of human atherosclerotic plaques	exploratory	Atherosclerosis	0.900	0.00	Human atherosclerotic plaque s	proposed	N/A
CSF Dynamic Biomarkers for Differential Diagnosis of NPH vs AD with Co	clinical	Alzheimer's Disease	0.900	0.50	aortic endothelial cells	proposed	$6,550,000
Senolytic Therapy (D+Q) Phase IIa Trial in Early Alzheimer's Disease	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Proposed experiment from debate on Synaptic pruning by microglia in ea	falsification	Alzheimer's Disease	0.400	0.50	mouse	proposed	$200,000
Proposed experiment from debate on Senolytics targeting p16/p21+ senes	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Biomechanical Impact Profiles and Chronic Traumatic Encephalopathy Phe	clinical	Neurodegeneration	0.400	0.50	in_silico	proposed	$180,000
Mechanism: Why Does Amyloid Removal Only Slow Decline 27%?	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Experiment: Autoimmune Hypothesis Testing in AD	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Experimental: CAAR-T Cell Therapy for Autoantibody-Mediated Neurotoxic	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
cGAS-STING Pathway Validation Study in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,100,000
Microglial Aging and Immune Memory in Neurodegeneration — Training the	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$2,960,000
Microglial Contributions to Huntington's Disease Pathogenesis	validation	Neuroinflammation	0.400	0.50	human	proposed	$2,960,000
Mixed Pathology Effects on Parkinson's Disease Progression and Treatme	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Proposed experiment from debate on Perivascular spaces and glymphatic	falsification	Neurodegeneration	0.400	0.50	mouse	proposed	$240,000
s:** - Test tau spreading in AQP4 knockout vs wild-type mice with PSP/	falsification	Neurodegeneration	0.400	0.50	mouse	proposed	$260,000
Proposed experiment from debate on Perivascular spaces and glymphatic	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
Glymphatic-Circadian Axis Enhancement Therapy for Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
CSF Dynamic Biomarkers for Differential Diagnosis of NPH vs AD with Co	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
NPH Glymphatic System Interaction Experiment	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
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 & PMID	Authors	Journal	Year	Citations
Aquaporin-4 in glymphatic system, and its implication for central nervous system [PMID:36796590]	Peng S, Liu J, Liang C, Yang L, Wang G	Neurobiol Dis	2023	2
Uncommon inflammatory/immune-related myelopathies. [PMID:34715593]	Valencia-Sanchez C, Flanagan EP	J Neuroimmunol	2021	2
Complement, Inflammasome, and Microglial Crosstalk in Glaucoma: From Neurodegene [PMID:41900887]	Chen TY, Wu N, Sun X	Life (Basel)	2026	1
Clinical, Immunological, and Vesicular Markers in Sarcopenia and Presarcopenia. [PMID:40917056]	Shuliko LM, Svarovsky DA, Spirina LV, Og	Front Biosci (Landmark Ed)	2025	1
CD47-blocking antibody interferes with neutrophil extracellular traps formation [PMID:39951937]	Diao Y, Hao M, Xie M, Hu X, Tan R, Wang	J Neuroimmunol	2025	1
Asparagine Endopeptidase Inhibition Attenuates Tissue Plasminogen Activator-Indu [PMID:40116141]	Xie G, Jiang G, Huang L, Sun S, Li X, Wu	CNS Neurosci Ther	2025	1
Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteost [PMID:40868276]	Voicu V, Toader C, Șerban M, Covache-Bus	Biomedicines	2025	1
Complement C1q/C3-CR3 signaling pathway mediates abnormal microglial phagocytosi [PMID:38642614]	Han QQ, Shen SY, Liang LF, Chen XR, Yu J	Brain Behav Immun	2024	1
Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1. [PMID:37384704]	Zhang T, Xu D, Trefts E, Lv M, Inuzuka H	Science	2023	1
Microglia regulation of synaptic plasticity and learning and memory. [PMID:34472455]	Cornell J, Salinas S, Huang HY, Zhou M	Neural Regen Res	2022	1
Glymphatic System Impairment in Alzheimer's Disease and Idiopathic Normal Pressu [PMID:31959516]	Reeves BC, Karimy JK, Kundishora AJ, Mes	Trends Mol Med	2020	1
Inebilizumab-cdon. [PMID:32936251]	Unknown	American journal of health-sys	2020	1
The glymphatic pathway in neurological disorders. [PMID:30353860]	Rasmussen MK, Mestre H, Nedergaard M	Lancet Neurol	2018	1
Complement and microglia mediate early synapse loss in Alzheimer mouse models. [PMID:27033548]	Hong S, Beja-Glasser VF, Nfonoyim BM, Fr	Science	2016	1
Panacis Quinquefolii Radix Polysaccharides Alleviate Depressive-Like Behaviors i [PMID:41914021]	Xie M, Feng L, Li R, Li M, Shen L, Zhang	CNS neuroscience & therapeutic	2026	0
Enhanced anticancer activity of nanoemulsified cardamom extract via modulation o [PMID:41658858]	["Soltani T", "Karimian M", "Vaziri H",	Biochemistry and biophysics re	2026	0
Vaccine-induced antibodies can limit Salmonella infection in the absence of comp [PMID:41738756]	Perez-Toledo M, Aksu-Istil K, Marcial-Ju	mBio	2026	0
β-Hydroxybutyrate improves glymphatic system function and alleviates cerebral ed [PMID:41535708]	Yu MJ, Xiong RQ, Wu JW, Li YC, Xie JX et	Acta Pharmacol Sin	2026	0
Neutrophil-microglia interaction drives motor dysfunction in a neuromyelitis opt [PMID:41665955]	Qi F, Lennon VA, Zhao S, Guo Y, Ding H e	J Clin Invest	2026	0
Safety and efficacy of ravulizumab in patients with NMOSD previously treated wit [PMID:41782198]	Bennett JL, Bhattacharyya S, Zabeti A, L	Mult Scler	2026	0

Debates (6)

Multi-agent debates referencing this entity

What are the mechanisms by which microglial senescence contributes to ALS pathol

active · Rounds: 6 · Score: 0.75 · 2026-04-26

Should metabolic reprogramming via SIRT1/NAD+/PGC-1alpha axis be prioritized to

closed · Rounds: 4 · Score: 0.81 · 2026-04-23

Investigate the therapeutic potential of clearing senescent cells (senolytics) t

closed · Rounds: 4 · Score: 0.75 · 2026-04-16

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

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

Senolytics targeting p16/p21+ senescent astrocytes and microglia may reduce SASP

closed · Rounds: 4 · Score: 0.89 · 2026-04-06

Senescent cell clearance as neurodegeneration therapy

closed · Rounds: 3 · Score: 0.95 · 2026-04-04

Related Research

Hypotheses and analyses mentioning SASP in their description or question text

SASP-Driven Aquaporin-4 Dysregulation

Score: 0.782 · neurodegeneration · 2026-04-02

## Mechanistic Overview SASP-Driven Aquaporin-4 Dysregulation starts from the claim that modulating AQP4 within the dise

TBK1 Loss Locks Microglia in an Aged/Senescent Transcriptional State, Fueling AL

Score: 0.776 · ALS · 2026-04-26

SASP-Mediated Cholinergic Synapse Disruption

Score: 0.763 · neurodegeneration · 2026-04-02

## Mechanistic Overview SASP-Mediated Cholinergic Synapse Disruption starts from the claim that modulating MMP2/MMP9 wit

Complement-SASP Amplification Cascade as Mechanistic Link

Score: 0.741 · neurodegeneration · 2026-04-16

**Molecular Mechanism and Rationale** The complement-SASP amplification cascade represents a mechanistic nexus where ce

SASP Secretome-based Molecular Distinction via CXCL1/CXCL2/MMP-3 Ratio

Score: 0.720 · neurodegeneration · 2026-04-22

## Mechanistic Overview SASP Secretome-based Molecular Distinction via CXCL1/CXCL2/MMP-3 Ratio starts from the claim tha

SASP-Secreted MMP-9 from Senescent Microglia Generates Pathological TDP-43 C-Ter

Score: 0.682 · ALS · 2026-04-26

TNF-α/IL-1β-Cx43 Hemichannel Axis as Upstream Link Between SASP and Synaptic Pru

Score: 0.663 · cell biology · 2026-04-13

## Mechanistic Overview TNF-α/IL-1β-Cx43 Hemichannel Axis as Upstream Link Between SASP and Synaptic Pruning starts from

SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs Calcium Sensing and

Score: 0.652 · neurodegeneration · 2026-04-16

## Mechanistic Overview SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs Calcium Sensing and Links Synaptic

NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Complement Amplification

Score: 0.592 · neurodegeneration · 2026-04-16

## Mechanistic Overview NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Complement Amplification starts from the

NLRP3 Inflammasome Blockade as Upstream Intervention to Prevent SASP Amplificati

Score: 0.566 · neurodegeneration · 2026-04-16

## Mechanistic Overview NLRP3 Inflammasome Blockade as Upstream Intervention to Prevent SASP Amplification starts from t

Timed Senolytic Therapy Eliminates p16^Ink4a/p21^Cip1-Senescent Microglia to Pre

Score: 0.564 · neuroinflammation · 2026-04-15

## Mechanistic Overview Timed Senolytic Therapy Eliminates p16^Ink4a/p21^Cip1-Senescent Microglia to Prevent SASP-Driven

H2: SASP Neutralization via JAK/STAT Inhibition Preserves Astrocyte Function

Score: 0.550 · neurodegeneration · 2026-04-22

## Mechanistic Overview H2: SASP Neutralization via JAK/STAT Inhibition Preserves Astrocyte Function starts from the cla

Combined NAMPT-Alectinib Targeting of SASP-Complement Cascade

Score: 0.549 · neuroinflammation · 2026-04-16

## Mechanistic Overview Combined NAMPT-Alectinib Targeting of SASP-Complement Cascade starts from the claim that modulat

NFκB/C1Q SASP Modulation for Synaptic Protection

Score: 0.534 · neurodegeneration · 2026-04-17

## Mechanistic Overview NFκB/C1Q SASP Modulation for Synaptic Protection starts from the claim that modulating not yet s

P2RY12 activation induces cellular senescence in cerebral VSMCs, driving neurode

Score: 0.373 · neurodegeneration · 2026-04-21

## Mechanistic Overview P2RY12 activation induces cellular senescence in cerebral VSMCs, driving neurodegeneration via S