Non-histone MACROH2A domain as an inhibitor of PARP-1 activity and its use

摘要

A nucleic enzyme inhibitor poly (adenosine 5'-diphospho-ribose) polymerase ["poly (ADP-ribose) polymerase 1 (PARP-1)"] for use as a medicine in the prevention or treatment of a disease associated with activation PARP-1 selected from the group comprising tissue damage resulting from cell damage or death due to necrosis or apoptosis, neural tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases, vascular stroke, cardiovascular disorders, degeneration age-related macular, AIDS, age-related immune diseases, arthritis, atherosclerosis, cachexia, cancer, degenerative striated muscle diseases involving replicative senescence, diabetes, head trauma, age-related immune diseases, inflammatory disorders, dystrophy muscle, osteoarthritis, osteoporosis, acute and / or chronic pain, renal failure, retinal ischemia, shock s eptidemic, skin aging, wherein said inhibitor has a phosphoesterase activity, and comprises an amino acid sequence of the non-histone domain of terminal C of a histone macroH2A selected from the group consisting of the non-histone domain of terminal C of human macroH2A1.1 (amino acids 121 to 369 of SEQ ID NO: 1), macroH2A1.2 (amino acids 120 to 371 of SEQ ID NO: 2), and macroH2A2 (amino acids 121 to 372 of SEQ ID NO: 3) histone.