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.

1016Connections

4Hypotheses

8Analyses

50Outgoing

50Incoming

2Experiments

9Debates

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	1016 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 (593)

Target	Relation	Type	Str
Replisome Protection	protects_against	process	0.95
Transcription-Replication Conflicts	regulates	process	0.95
replisome	protects_against	protein	0.95
TIMELESS	interacts_with	protein	0.90
DOT1L	interacts_with	protein	0.90
transcription-replication conflicts	suppresses	process	0.90
Transcription-Replication Conflicts	protects_against	process	0.90
Transcription	regulates	process	0.90
PARP inhibitor	therapeutic_target	drug	0.90
TIMELESS	functions_together_with	gene	0.90
Replisome Protection	involved_in	process	0.90
TIPIN	interacts_with	protein	0.90
TIPIN	functions_together_with	gene	0.90
DNA DAMAGE RESPONSE	involved_in	entity	0.90
DNA repair	mediates	process	0.90
DOT1L	associated_with	protein	0.90
USP1	deubiquitinates	protein	0.90
Ovarian Cancer	associated_with	disease	0.90
OVARIAN CANCER	therapeutic_target	entity	0.90
Blood-Brain Barrier Damage	involved_in	phenotype	0.88
PARylation	mediates	process	0.88
chromatin trapping	mediates	process	0.86
blood-brain barrier	involved_in	cell_type	0.85
Homologous Recombination	involved_in	pathway	0.85
BLOOD-BRAIN BARRIER	regulates	entity	0.85
Replisome Protection	mediates	process	0.85
aging-induced blood-brain barrier damage	mediates	phenotype	0.85
Dna Damage	involved_in	process	0.85
Parpi Resistance	contributes_to	phenotype	0.85
Apoptosis	mediates	process	0.85
K63-Linked Polyubiquitination	involved_in	process	0.85
Dna Damage Repair	involved_in	process	0.85
PARYLATION	regulates	process	0.80
autophagy disorder	involved_in	biological_process	0.80
pathological protein aggregation	involved_in	biological_process	0.80
blood-brain barrier damage	involved_in	biological_process	0.80
DNA damage	activates	biological_process	0.80
NAD metabolism	involved_in	pathway	0.80
neuronal cell death	causes	biological_process	0.80
PARthanatos	activates	biological_process	0.80
NAD+	regulates	metabolite	0.80
DNA REPAIR	involved_in	entity	0.80
PARylation	regulates	process	0.80
Dna Damage	traps	process	0.80
apoptosis pathway	participates_in	pathway	0.80
DNA Double-Strand Breaks	involved_in	process	0.80
amyotrophic lateral sclerosis	implicated_in	disease	0.80
Huntington's disease	implicated_in	disease	0.80
Parkinson's disease	implicated_in	disease	0.80
PARP1_protein	encodes	protein	0.80

Incoming (423)

Source	Relation	Type	Str
USP1	interacts_with	entity	0.95
USP1	regulates	entity	0.95
SNCA	activates	gene	0.90
USP1	degrades	protein	0.90
h-69919c49	targets	hypothesis	0.90
Parp Inhibitors	targets	drug	0.90
USP1	associated_with	gene	0.90
CX43	interacts_with	protein	0.85
K63-linked Polyubiquitination	regulates	process	0.85
MAPK8	phosphorylates	protein	0.85
UBIQUITIN	binds_to	entity	0.85
UFL1	phosphorylates	gene	0.85
K63-linked Polyubiquitination	modulates	mechanism	0.85
Parp Inhibitors	inhibits	drug	0.85
KDM5A	interacts_with	gene	0.80
GJA1	interacts_with	gene	0.80
DNA	disrupts	gene	0.80
DNA	regulates	gene	0.80
CX43	inhibits	gene	0.80
PARPi	activates	drug	0.80
cGAS	interacts_with	protein	0.80
CGAS	interacts_with	gene	0.80
ANTHOCYANINS	inhibits	compound	0.80
NECROPTOSIS	activates	pathway	0.70
IBA1	activates	gene	0.70
NLRP3	activates	gene	0.70
GFAP	activates	gene	0.70
MICROGLIA	associated_with	cell_type	0.70
FUS	activates	gene	0.70
MMP9	expressed_in	gene	0.70
ACHE	activates	gene	0.70
AMPK	activates	gene	0.70
ATG5	activates	gene	0.70
LRRK2	associated_with	gene	0.70
HTT	interacts_with	gene	0.70
HIF1A	activates	gene	0.70
ENDOTHELIAL	activates	cell_type	0.70
BECN1	activates	gene	0.70
ATG7	activates	gene	0.70
ACHE	inhibits	gene	0.70
NLRP3	associated_with	gene	0.70
NEURONS	activates	cell_type	0.70
NFKB	inhibits	gene	0.70
IGF1	activates	gene	0.70
CASP3	interacts_with	gene	0.70
OXIDATIVE STRESS	causes	phenotype	0.70
HUNTINGTON	inhibits	disease	0.70
CGAS	inhibits	gene	0.70
TDP-43	interacts_with	gene	0.70
BRCA2	inhibits	gene	0.70

Targeting Hypotheses (4)

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

Mentioning Analyses (8)

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	proposed	$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 (9)

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 (593)

Incoming (423)

Targeting Hypotheses (4)

Mentioning Analyses (8)

What upstream mechanisms trigger p53 activation specifically in response to poly

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)

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 (9)

The abstract shows p53 is a central regulator of C9orf72-mediated neurodegenerat

TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small

TDP-43 phase separation therapeutics for ALS-FTD

Epigenetic reprogramming in aging neurons

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

Epigenetic clocks and biological aging in neurodegeneration

What cell types are most vulnerable in Alzheimers Disease based on SEA-AD transc

What cell types are most vulnerable in Alzheimer's Disease based on SEA-AD trans

Cell-type specific expression patterns of neurodegeneration genes in SEA-AD

Related Research