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A broad range of peptides protect the brain from injury. Among these is vaso-active intestinal peptide (VIP), a 28-amino acid peptide originally isolated from intestinal extracts, also widely distributed in the peripheral and central nervous systems (PNS and CNS). With aging, reduced brain VIP expression leads to memory loss, learning problems and impaired sexual function. Another activity-dependent neuroprotective protein (ADNP) is crucial for brain development and might protect against head injury. Studies on these and other peptides are opening up new horizons in our understanding of nerve cell survival and death, with respect to brain development, acquisition of learning abilities, and age–related memory and other brain-function loss. Cooperation Profs. Gozes and Brenneman studied a range of peptides protecting the brain from injury. Prof. Gozes’s group focused on molecular cloning of these peptides, while Prof. Brenneman, who was at NIH during the period of the BSF grant, concentrated on assay development and in vitro pharmacological testing. As an exemplary piece of research, in both cooperation and scientific results, this project was awarded the annual BSF’s Neufeld Award (LINK) for the best proposal in the Health Sciences in 1999. Findings Prof. Brenneman identified several novel brain proteins regulated by VIP. These include Activity-Dependent Neurotrophic Factor (ADNF), which can prevent neuronal cell death mediated by the β-A peptide that has been implicated in AD (Alzheimer’s Disease), and by the toxic AIDS protein gp120. Prof. Gozes and Brenneman also identified and cloned ADNP, which contains the small NAP peptide. “Knocking out” this factor was found to be lethal during early brain development. These novel brain peptides also have therapeutic potential, particularly in AD and other NDD (neurodegenerative diseases). Recognizing its therapeutic potential, the new biotechnology company Allon Therapeutics in Vancouver, Canada, is now carrying out extensive Phase-II clinical trials of NAP for mild cognitive impairment in various NDD. Since Prof. Brenneman left the academic world to work in the pharmaceutical industry, Prof. Gozes in now continuing collaboration along these lines with Dr. Joanna Hill and Dr. Peng Loh from the NIH.
PREVENTING FETAL HYPOXIC BRAIN DAMAGE Dr. Hava Golan: Department of Molecular Genetics, Ben Gurion University, Beer Sheva
"Our groups have been studying the influence of pre-natal hypoxia for several years, addressing the rational design of preventive treatments based on accumulated knowledge in the literature. The support received from the BSF grant enabled us to carry out wide screening of changes in the expression of the whole genome. A definitive analysis, based on state-of-the-art bio-informatics approaches, is in progress, in collaboration with Dr. Vered Chalifa Caspi, National Institute for Biotechnology in the Negev. This joint effort has already highlighted major changes in several signaling pathways critical for correct brain development, which will be further studied in our group in the future. The BSF grant is allowing us to develop and evaluate rational strategies for treating infants at risk due to hypoxic events experienced prior to or during delivery."
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