PARP
The double-edged DNA repair enzyme. PARP (Poly ADP-Ribose Polymerase) detects and repairs DNA damage—essential for survival. But each repair consumes NAD+. Chronic DNA damage leads to PARP overactivation, depleting cellular energy and accelerating aging. Understanding PARP illuminates the NAD+ depletion problem.
How PARP Works
Damage Detection
PARP1 senses DNA strand breaks. First responder to damage.
PAR Chain Building
Uses NAD+ to build poly(ADP-ribose) chains. Signals repair machinery.
Repair Recruitment
PAR chains recruit repair proteins to damage site.
NAD+ Consumption
Each repair event consumes NAD+. Heavy damage = massive depletion.
Energy Crisis
NAD+ needed for energy. Depletion causes cell dysfunction or death.
Parthanatos
Excessive PARP activation triggers cell death. Unique death pathway.
What Causes PARP Overactivation
Oxidative Stress
Free radicals damage DNA. Chronic oxidative stress = chronic PARP activation.
Inflammation
Inflammatory mediators cause DNA damage. PARP responds constantly.
Aging
Accumulated damage. PARP more active with age. NAD+ drops.
UV/Radiation
Direct DNA damage. Sun exposure, environmental radiation.
PARP Inhibitors in Cancer
Mechanism
Block PARP repair in cancer cells. Works especially in BRCA mutations where backup repair also defective.
Synthetic Lethality
Cancer cells with defective BRCA can't survive without PARP too. Normal cells have backup.