Humanin (HN) and HN-derived peptides comprise a family of bioactive molecules (HN-peptides) with potent neuroprotective activity. More specifically, HN, first member of the family, was discovered in 2001 as the product (MAPRGFSCLLLLTSEIDLPVKRRA) of a cDNA library, constructed from the occipital lobe of an Alzheimer's brain, and found to suppress the in vitro neuronal cell death caused by early onset Familial Alzheimer's Disease genes, the beta-amyloid peptide (main constituent of the toxic amyloid plaques) and the anti-Amyloid Precursor Protein (anti-APP) antibody [Hasimoto et al., PNAS 2001, 98:6336]. Neuroprotective activity of HN-peptides is closely related with their primary structure. Among the most potent of them are HN-[Gly14], having a Gly- residue in the place of Ser14, and Colivelin, a "hybrid" peptide (SALLRSIPAPAGASRLLLLTGEIDLP) produced by the combination of the Activity-Dependent-Neurotrophic-Factor-9 (SALLRSIPA) and the active core of HN, suitably transformed (PAGASRLLLLTGEIDLP). In addition to in vitro activity, various HN-peptides were evaluated in in vivo behavioral tests and found to improve experimentally induced impairment of spatial orientation and memory in rats and mice.
Almost ten years after their discovery, the exact mechanism of action, putative receptors, interaction sites with cells and tissues, bioavailability and biodistribution, putative entrance to the brain, etc., of HN and HN-derived peptides are still a matter of discussion. Ultimate goal of relevant research is to gather more information concerning the mode through which these peptides exert their neuroprotective action as well as to explore the perspectives of developing new tools against neurodegenerative diseases. In this respect, some previous and recent research results of ours, concerning solid-phase synthesis of new HN-peptides [Evangelou et al., J. Peptide Sci. 2004, 10:631], structural studies with NMR and CD analysis [Benaki et al., BBRC 2005, 329:152; Benaki et al., BBRC 2006, 349:634], labeling with radioisotopes, in vitro stability and cell binding as well as in vivo biodistribution and neuroprotective activity studies [Kunesova et al., Peptides 2008, 29:1982; Evangelou et al., Peptides 2009, 30:2409] will be presented and discussed.
Speaker: E. Livaniou
Researcher A, Institute of Radioisotopes & Radiodiagnostic Products, NCSR "Demokritos"
Time: Monday, 3 May 2010, 13:00