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11. News on PARP-1, Something More to Study

W. Lee Kraus and colleagueW. Lee Kraus, Pharmacology, Weill Cornell Medical College, and Molecular Biology and Genetics, and his research group discovered that an important cellular enzyme poly (ADP-ribose) polymerase-1 (PARP-1) plays a pivotal role in gene transcription, which could lead to new cancer and neurological disease therapies. The researchers have characterized a whole new activity for the long-studied protein. They found that PARP-1 converts DNA from an active to a silent state, which brings forth the question of what genes are affected and whether the genes that are up-regulated or down-regulated in a disease can be targeted with PARP-1 to turn the genes on or off. PARP-1 is the most abundantly expressed member of a family of proteins long known to be involved in the metabolism of nicotinamide adenine dinucleotide (NAD+), a cellular co-factor involved in both energy use and signaling within cells. By the manipulation of the NAD+/PARP-1 mechanism, scientists may find new pharmacological ways of switching genes on and off at will. In addition to the implications that PARP-1 may play a role in cancer, which is driven by genetic abnormalities, recent studies have found that inhibition of PARP-1 activity is associated with neurological and learning impairment, and it also has been implicated in immune responses, diabetes, and aging. There is the possibility that the NAD+/PARP-1 system may connect daily diet to genetic activity within cells.

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