NAP mechanisms of neuroprotection.
An 8-amino-acid peptide, NAPVSIPQ (NAP), was identified as the smallest active element of activity-dependent neuroprotective protein that exhibits potent neuroprotective action. Potential signal transduction pathways include cGMP production and interference with inflammatory mechanisms, tumor necrosis factor-alpha, and MAC1-related changes. Because of its intrinsic structure, NAP might interact with extracellular proteins and also transverse membranes. NAP-associated protection against oxidative stress, glucose deprivation, and apoptotic mechanisms suggests interference with fundamental processes. This paper identifies p53, a key regulator of cellular apoptosis, as an intracellular target for NAP's activity.
Gozes
Illana
I
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. igozes@post.tau.ac.il
Steingart
Ruth A
RA
Spier
Avron D
AD
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control; D006152:Cyclic GMP / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004660:Encephalitis / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D016177:Macrophage-1 Antigen / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000378:metabolism
D016177:Macrophage-1 Antigen; D018696:Neuroprotective Agents; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C425904:davunetide; D006152:Cyclic GMP