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.

905Connections

3Hypotheses

6Analyses

50Outgoing

50Incoming

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
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
DNA Damage Detection	Binds to single-strand and double-strand DNA breaks
Associated Diseases	AD, ALI, ALS, ALZHEIMER, AMI, ARM
Known Drugs/Compounds	OLAPARIB, PARP inhibitor, Parp Inhibitors, EMPAGLIFLOZIN, ANTHOCYANINS, TREHALOSE
Interactions	PEN2, PSEN1, DAPK1, HSPG2, IL1B, APP
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	905 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure: PARP1 — PDB 4DQY Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Wiki Pages (21)

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 (576)

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

Incoming (329)

Source	Relation	Type	Str
USP1	interacts_with	entity	0.95
USP1	regulates	entity	0.95
SNCA	activates	gene	0.90
Parp Inhibitors	targets	drug	0.90
USP1	binds	protein	0.90
USP1	degrades	protein	0.90
USP1	deubiquitinates	gene	0.90
USP1	associated_with	gene	0.90
h-69919c49	targets_gene	hypothesis	0.90
K63-linked Polyubiquitination	regulates	process	0.85
MAPK8	phosphorylates	protein	0.85
UBIQUITIN	binds_to	entity	0.85
K63-linked Polyubiquitination	modulates	mechanism	0.85
Parp Inhibitors	inhibits	drug	0.85
CX43	interacts_with	protein	0.85
UFL1	phosphorylates	gene	0.85
h-69919c49	targets	hypothesis	0.80
KDM5A	interacts_with	gene	0.80
GJA1	interacts_with	gene	0.80
ANTHOCYANINS	inhibits	compound	0.80
cGAS	interacts_with	protein	0.80
DNA	disrupts	gene	0.80
DNA	regulates	gene	0.80
PARPi	activates	drug	0.80
CX43	inhibits	gene	0.80
CGAS	suppresses	gene	0.70
TDP-43	interacts_with	gene	0.70
BRCA2	inhibits	gene	0.70
BRCA1	inhibits	gene	0.70
HUNTINGTON	inhibits	disease	0.70
OXIDATIVE STRESS	causes	phenotype	0.70
CSF1R	associated_with	gene	0.65
BDNF	associated_with	gene	0.65
NGF	associated_with	gene	0.65
DLG4	associated_with	gene	0.65
CD38	reduces	gene	0.65
CAMK2A	activates	gene	0.65
BACE1	co_discussed	gene	0.65
CTSD	co_discussed	gene	0.65
MBP	co_discussed	gene	0.65
MTOR	co_discussed	gene	0.65
OLIG2	co_discussed	gene	0.65
CR1	co_discussed	gene	0.65
EMPAGLIFLOZIN	activates	drug	0.65
UBIQUITIN	promotes	gene	0.65
APP	inhibits	gene	0.65
CGAS	recruits	gene	0.65
PARKINSON	associated_with	gene	0.65
TUMOR CELLS	inhibits	cell_type	0.65
APOPTOSIS	causes	phenotype	0.65

Targeting Hypotheses (3)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
PARP1 Inhibition Therapy	0.575	neurodegeneration	TDP-43 phase separation therapeutics for
PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Su	0.562	neurodegeneration	What upstream mechanisms trigger p53 act
Oligodendrocyte DNA Repair Enhancement	0.378	neurodegeneration	Cell type vulnerability in Alzheimers Di

Mentioning Analyses (6)

Scientific analyses that reference this entity

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
Design, synthesis and biological evaluation of novel pyrrolo[1,2-b]pyridazin-2(1 [PMID:41672027]	He Q, He J, Huan X, Song S, Zhang X et a	Eur J Med Chem	2026	0
Molecular and Antiangiogenic Effects of Paclitaxel-Loaded Nanoparticles: Influen [PMID:41790974]	Passos JS, de Melo GB, Salata GC, Machad	Mol Pharm	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 JP, 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
Effective oral countermeasures against ionizing radiation-induced damage without [PMID:41946301]	López-Blanch R, Oriol-Caballo M, Salvado	Biomed Pharmacother	2026	0
Hepatic GAL1 deficiency alleviates steatosis via WWP2-mediated PARP1 degradation [PMID:41951010]	Li Y, Li R, Wang P, Xu J, Zhang C et al.	Biochim Biophys Acta Mol Basis	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

PARP1

Understanding Entity Pages

Summary

Wiki Pages (21)

PARP1 Gene

cbs-psp-daily-action-plan

Personalized Treatment Plan — Atypical Parkinsonism (CBS/PSP)

Parthanatos in Neurodegeneration

nimodipine-als

NPM1 Gene

Pathway Diagram

Outgoing (576)

Incoming (329)

Targeting Hypotheses (3)

Mentioning Analyses (6)

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

TDP-43 phase separation therapeutics for ALS-FTD

Related Papers (20)

PARP1

Understanding Entity Pages

Summary

Wiki Pages (21)

PARP1 Gene

cbs-psp-daily-action-plan

Personalized Treatment Plan — Atypical Parkinsonism (CBS/PSP)

Parthanatos in Neurodegeneration

nimodipine-als

NPM1 Gene

oxidative-stress-comparison

Section 153: Virtual Reality Therapy Protocols in CBS/PSP

DNA Damage Response in Corticobasal Syndrome

Epigenetic-Metabolic Coupling: SIRT1 Activator + NAD+ Precursor

DNA Damage Response Impairment Pathway

NAD+ Precursors for Neurodegeneration

dna-damage-repair

amiloride-als

PSEN2 — Presenilin 2

DNA Damage Response in Alzheimer's Disease

nct06365190-rtms-pd

Riluzole ALS Trials

AIFM1 Gene

Cockayne Syndrome

Apoptosis in Neurodegeneration

Pathway Diagram

Outgoing (576)

Incoming (329)

Targeting Hypotheses (3)

Mentioning Analyses (6)

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

TDP-43 phase separation therapeutics for ALS-FTD

Related Papers (20)