TY - JOUR T1 - PolyADP-Ribosylation Is Involved in Neurotrophic Activity JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7420 LP - 7428 DO - 10.1523/JNEUROSCI.0333-05.2005 VL - 25 IS - 32 AU - Leonid Visochek AU - Ruth A. Steingart AU - Ina Vulih-Shultzman AU - Rodica Klein AU - Esther Priel AU - Illana Gozes AU - Malka Cohen-Armon Y1 - 2005/08/10 UR - http://www.jneurosci.org/content/25/32/7420.abstract N2 - PolyADP-ribosylation is a transient posttranslational modification of proteins, mainly catalyzed by poly(ADP-ribose)polymerase-1 (PARP-1). This highly conserved nuclear protein is activated rapidly in response to DNA nick formation and promotes a fast DNA repair. Here, we examine a possible association between polyADP-ribosylation and the activity of neurotrophins and neuroprotective peptides taking part in life-or-death decisions in mammalian neurons. The presented results indicate an alternative mode of PARP-1 activation in the absence of DNA damage by neurotrophin-induced signaling mechanisms. PARP-1 was activated in rat cerebral cortical neurons briefly exposed to NGF-related nerve growth factors and to the neuroprotective peptides NAP (the peptide NAPVSIPQ, derived from the activity-dependent neuroprotective protein ADNP) and ADNF-9 (the peptide SALLRSIPA, derived from the activity-dependent neurotrophic factor ADNF) In addition, polyADP-ribosylation was involved in the neurotrophic activity of NGF-induced and NAP-induced neurite outgrowth in differentiating pheochromocytoma 12 cells as well as in the neuroprotective activity of NAP in neurons treated with the Alzheimer's disease neurotoxin β-amyloid. A fast loosening of the highly condensed chromatin structure by polyADP-ribosylation of histone H1, which renders DNA accessible to transcription and repair, may underlie the role of polyADP-ribosylation in neurotrophic activity. ER -