gene

PARP1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about PARP1: 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.

1031Connections

5Hypotheses

14Analyses

50Outgoing

50Incoming

2Experiments

20Debates

Summary

Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme involved in DNA repair, genomic stability, and cell death pathways. Overactivation contributes to neurodegeneration through NAD+ depletion and parthanatos. Target for neuroprotective therapies in Parkinson and Alzheimer diseases.

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🧬 Gene Info

Gene Symbol	PARP1
Aliases	Poly(ADP-ribose) polymerase 1, ADPRT, Poly(ADP-Ribose
Protein Family	PARP family (17 members)
Protein Type	Enzyme
Target Class	Enzyme
Function	Upon DNA binding, PARP1 catalytic activity increases 500-fold, synthesizing PAR chains on itself (automodification) and target proteins[@benjamin1980].
Mechanism of Action	Competitive inhibitors of PARP1 enzymatic activity blocking DNA repair
Subcellular Localization	** Nucleus (primary), mitochondrial under stress
Druggability	Medium (0.62)
Clinical Stage	Approved
Molecular Weight	113 kDa
Pathways	DNA repair, NAD+ metabolism, Apoptosis, NF-κB
UniProt ID	P09874
GeneCards	PARP1
Human Protein Atlas	PARP1
Associated Diseases	AD, Aging, ALI, Als, Alzheimer
Known Drugs/Compounds	ANTHOCYANINS, EMPAGLIFLOZIN, OLAPARIB, PARPi, PARP inhibitor, Parp Inhibitors
Interactions	A2M, AARS1, ABCG1, ACHE, AD, AGING
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	PARP1 Inhibition Therapy PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Dam Oligodendrocyte DNA Repair Enhancement
KG Connections	1030 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — PARP1 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

4DQY — X-ray / Cryo-EM

🔮 AI Predicted Structure

P09874 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (4)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    DNA["DNA Damage"] -->|"Activates"| PARP1["PARP1 Enzyme"]
    PARP1 -->|"Catalyzes"| PAR["PAR Chain Synthesis"]
    PAR -->|"Recruits"| Repair["DNA Repair Proteins"]
    PARP1 -.Overactivation.-> NAD["NAD+ Depletion"]
    NAD -->|"Impairs"| Mito["Mitochondrial Function"]
    Mito -->|"Reduces"| ATP["ATP Production"]
    ATP -.Depletion.-> Death["Cell Death"]
    PARP1 -->|"Modulates"| Inflammation["Neuroinflammation"]
    PARP1 -.Inhibition therapeutic in.-> AD["Alzheimer's Disease"]

Outgoing (604)

Target	Relation	Type	Str
PARP1	encodes	protein	0.00
Replisome Protection	protects_against	process	0.95
Transcription-Replication Conflicts	regulates	process	0.95
replisome	protects_against	protein	0.95
OVARIAN CANCER	therapeutic_target	entity	0.90
transcription-replication conflicts	suppresses	process	0.90
PARP inhibitor	therapeutic_target	drug	0.90
TIMELESS	interacts_with	protein	0.90
Transcription-Replication Conflicts	protects_against	process	0.90
DOT1L	interacts_with	protein	0.90
TIPIN	interacts_with	protein	0.90
Replisome Protection	involved_in	process	0.90
DNA DAMAGE RESPONSE	involved_in	entity	0.90
NAD+	causes	metabolite	0.90
USP1	deubiquitinates	protein	0.90
TIPIN	functions_together_with	gene	0.90
TIMELESS	functions_together_with	gene	0.90
DOT1L	associated_with	protein	0.90
DNA repair	mediates	process	0.90
Transcription	regulates	process	0.90
Ovarian Cancer	associated_with	disease	0.90
DNA Repair	regulates	phenotype	0.90
PARylation	mediates	process	0.88
Blood-Brain Barrier Damage	involved_in	phenotype	0.88
chromatin trapping	mediates	process	0.86
aging-induced blood-brain barrier damage	mediates	phenotype	0.85
Replisome Protection	mediates	process	0.85
Apoptosis	mediates	process	0.85
Dna Damage	involved_in	process	0.85
blood-brain barrier	involved_in	cell_type	0.85
Dna Damage Repair	involved_in	process	0.85
K63-Linked Polyubiquitination	involved_in	process	0.85
Parpi Resistance	contributes_to	phenotype	0.85
Homologous Recombination	involved_in	pathway	0.85
BLOOD-BRAIN BARRIER	regulates	entity	0.85
DNA REPAIR	involved_in	pathway	0.80
DNA Double-Strand Breaks	involved_in	process	0.80
Huntington's disease	implicated_in	disease	0.80
Parkinson's disease	implicated_in	disease	0.80
amyotrophic lateral sclerosis	implicated_in	disease	0.80
NAD metabolism	involved_in	pathway	0.80
neuronal cell death	causes	process	0.80
blood-brain barrier damage	involved_in	process	0.80
PARylation	regulates	process	0.80
PARthanatos	activates	process	0.80
apoptosis pathway	participates_in	pathway	0.80
Dna Damage	traps	process	0.80
PARYLATION	regulates	process	0.80
pathological protein aggregation	involved_in	process	0.80
autophagy disorder	involved_in	process	0.80

Incoming (427)

Source	Relation	Type	Str
PARP1	encodes	gene	0.00
USP1	interacts_with	entity	0.95
USP1	regulates	entity	0.95
USP1	degrades	protein	0.90
h-69919c49	targets	hypothesis	0.90
SNCA	activates	gene	0.90
USP1	associated_with	gene	0.90
Parp Inhibitors	targets	drug	0.90
oxidative DNA damage	activates	phenotype	0.90
DNA damage	activates	process	0.90
UBIQUITIN	binds_to	entity	0.85
K63-linked Polyubiquitination	modulates	mechanism	0.85
UFL1	phosphorylates	gene	0.85
K63-linked Polyubiquitination	regulates	process	0.85
MAPK8	phosphorylates	protein	0.85
Parp Inhibitors	inhibits	drug	0.85
CX43	interacts_with	protein	0.85
KDM5A	interacts_with	gene	0.80
CX43	inhibits	gene	0.80
PARPi	activates	drug	0.80
DNA	disrupts	gene	0.80
CGAS	interacts_with	gene	0.80
cGAS	interacts_with	protein	0.80
GJA1	interacts_with	gene	0.80
DNA	regulates	gene	0.80
ANTHOCYANINS	inhibits	compound	0.80
FUS	activates	gene	0.70
HIF1A	activates	gene	0.70
ATG7	activates	gene	0.70
ACHE	activates	gene	0.70
ATG5	activates	gene	0.70
NEURONS	activates	cell_type	0.70
ENDOTHELIAL	activates	cell_type	0.70
IGF1	activates	gene	0.70
BECN1	activates	gene	0.70
NFKB	inhibits	gene	0.70
AMPK	activates	gene	0.70
MICROGLIA	associated_with	cell_type	0.70
ACHE	inhibits	gene	0.70
NLRP3	activates	gene	0.70
GFAP	activates	gene	0.70
NLRP3	associated_with	gene	0.70
NECROPTOSIS	activates	pathway	0.70
IBA1	activates	gene	0.70
HTT	interacts_with	gene	0.70
LRRK2	associated_with	gene	0.70
MMP9	expressed_in	gene	0.70
BRCA1	inhibits	gene	0.70
OXIDATIVE STRESS	causes	phenotype	0.70
CASP3	interacts_with	gene	0.70

Targeting Hypotheses (5)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
PARP1-NAD+-AIF bioenergetic collapse drives a self-amplifyin	0.760	neurodegeneration	What mechanisms drive the self-amplifyin
PARP1 Inhibition Therapy	0.738	neurodegeneration	TDP-43 phase separation therapeutics for
PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Su	0.661	neurodegeneration	What upstream mechanisms trigger p53 act
Oligodendrocyte DNA Repair Enhancement	0.550	neurodegeneration	Cell type vulnerability in Alzheimers Di
CD38 Inhibition to Preserve NAD+ Pools and Prevent PARP1-Med	0.380	metabolomics	Metabolomic signatures of neurodegenerat

Mentioning Analyses (14)

Scientific analyses that reference this entity

Experiments (2)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
DNA Damage Repair Deficiency Validation Study in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	completed	$7,500,000
Regulated Necrosis Validation Study in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Transcription-replication conflicts underlie sensitivity to PARP inhibitors. [PMID:38509368]	Petropoulos M, Karamichali A, Rossetti G	Nature	2024	1
PARP1-DOT1L transcription axis drives acquired resistance to PARP inhibitor in o [PMID:38778348]	Liu C, Li J, Xu F, Chen L, Ni M, Wu J, Z	Mol Cancer	2024	1
USP1 deubiquitinates PARP1 to regulate its trapping and PARylation activity. [PMID:39536107]	Nespolo A, Stefenatti L, Pellarin I, Gam	Sci Adv	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
Nuclear cGAS suppresses DNA repair and promotes tumorigenesis. [PMID:30356214]	Liu H, Zhang H, Wu X, Ma D, Wu J, Wang L	Nature	2018	1
Defective DNA Damage Response Is a Targetable Therapeutic Vulnerability in ESR1- [PMID:41499130]	Herzog SK, Stevens JH, Gu G, Grimm SL, C	Cancer Res	2026	0
Replicative gaps in DNA damage tolerance, genome instability, and cancer therapy [PMID:41864203]	Falbo L, Costanzo V	Mol Cell	2026	0
Versatile and sensitive detection of mono- and poly(ADP-ribosyl)ation reveals XR [PMID:41922367]	Dauben H, Mihaljević M, Kolvenbach A, Pa	Nat Commun	2026	0
Differential proteomic responses to short-term heat stress in Vechur and crossbr [PMID:41931203]	Anisha J P; Shynu M; Radhika G; Beena V;	Tropical animal health and pro	2026	0
Differential sensitivity of MCPH1- and BRCA2-deficient cancer cells to PARP-1 in [PMID:41931484]	Chapman IG, Wu X, Veuger S, Jowsey PA	PLoS One	2026	0
Targeting Poly (ADP-Ribose) Polymerase-1 for the Treatment of Neurodegenerative [PMID:41178110]	Polk S, Rassaeikashuk M, Thilagavathi R,	Chemical biology & drug design	2025	0
Increased nucleotide metabolism alleviates Alzheimer's disease pathology. [PMID:41102145]	["Yu Y", "Miller M", "Huang A", "Tan B",	Cell death & disease	2025	0
Roles and therapeutic potential of PARP-1 in neurodegenerative diseases. [PMID:41022359]	["Liu C", "Lai F", "Zhang T", "Mao K", "	Biochemical pharmacology	2025	0
Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and n [PMID:40905723]	Peng C, Maiuri T, Truant R	Journal of Huntington's diseas	2025	0
Targeting KCNN4 channels modulates microglial activation and apoptosis in a PD-r [PMID:40913912]	["Hung H", "Li I", "Lin Y", "Yeh T", "Ng	Biomedicine & pharmacotherapy	2025	0
Clinical approaches to overcome PARP inhibitor resistance. [PMID:40442774]	["Zou Y", "Zhang H", "Chen P", "Tang J",	Molecular cancer	2025	0
PARPs and PARP inhibitors: molecular mechanisms and clinical applications. [PMID:41460301]	Wang F, Guo Z, Carr MJ, Shi W	Molecular biomedicine	2025	0
Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated G [PMID:39480453]	["Sarkaria J", "Ballman K", "Kizilbash S	JAMA oncology	2024	0
PARP Inhibitors for Breast Cancer Treatment: A Review. [PMID:38512229]	["Morganti S", "Marra A", "De Angelis C"	JAMA oncology	2024	0
Blocking the Self-Destruct Program of Dopamine Neurons through Macrophage Migrat [PMID:38396375]	["Patel J", "Dawson V", "Dawson T"]	Movement disorders : official	2024	0

Debates (20)

Multi-agent debates referencing this entity

Related Research

Hypotheses and analyses mentioning PARP1 in their description or question text

No additional research found

PARP1

Understanding Entity Pages

Summary

Wiki Pages (4)

PARP1 (Poly(ADP-Ribose) Polymerase 1)

PARP1 Inhibition for Parthanatos Prevention in Neurodegeneration

PARP1 Gene

PARP1 Protein

Pathway Diagram

Outgoing (604)

Incoming (427)

Targeting Hypotheses (5)

Mentioning Analyses (14)

What mechanisms drive the self-amplifying vicious cycle linking oxidative stress

test

Metabolomic signatures of neurodegeneration: metabolic reprogramming in aging br

What upstream mechanisms trigger p53 activation specifically in response to poly

Do oligodendrocytes require DNA repair enhancement or inhibition for neuroprotec

Metabolomic signatures of neurodegeneration and energy metabolism dysfunction

Epigenetic reprogramming in aging neurons

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Epigenetic clocks and biological aging in neurodegeneration

Senolytic therapy for age-related neurodegeneration

TDP-43 phase separation therapeutics for ALS-FTD

Experiments (2)

Related Papers (20)

Debates (20)

Second debate: Microglial TREM2-SYK Pathway Enhancement

Debate: Chromatin Remodeling-Mediated Nutrient Sensing Restoration

Debate: LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Primin

Debate: ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE P

Debate: LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability i

Debate: ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes

Should '40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Sele

Should 'ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matt

Hypothesis debate: Nutrient-Sensing Epigenetic Circuit Reactivation

Hypothesis debate: SASP-Mediated Complement Cascade Amplification

Related Research