PARP1 and neurodegenerative disease: However, PARP activity is also connected to a variety of human diseases, essentially in two different ways: 1) in cancer, the repair of DNA damage allows cells to survive and possibly contributes to cancerogenesis; 2) in neurodegenerative diseases, excessive activation of PARP may deplete cellular substrates and lead to a specific form of programmed cell death, termed PARthanatos2.