Humanins, the neuroprotective and cytoprotective peptides with antiapoptotic and anti-inflammatory properties

Humanin (FIN) is a newly discovered 24-amino acid peptide, which may suppress neuronal cell death. FIN cDNA includes an open reading frame (HN-ORF) of 75 bases located 950 bases downstream of the 5' end of the FIN cDNA. It has been demonstrated that HN cDNA is 99% identical to the mitochondrial DNA (mtDNA) sequence. HIM homologs have been identified as expressed sequence tags (ESTs) in both rats and nematodes. Certain regions that are homologous to the FIN cDNA exist on human chromosomes. HN forms homodimers and multimers and this action seems to be essential for peptide function. HIM acts as a ligand for formyl peptide receptor-like 1 (FPRL1) and 2 (FPRL2). It has been demonstrated that FIN plays a protective role through its antiapoptotic activity that interferes with Bax activation, which suppresses Bax-dependent apoptosis. FIN has also been shown to suppress the c-Jun N-terminal kinase (JNK) and ASK/JNK-mediated neuronal cell death. Several studies have also confirmed that HN could be important in the prevention of angiopathy-associated Alzheimer 's disease dementia, diseases related to mitochondrial dysfunction (MELAS), and other types of P-amyloid accumulation-associated neurodegeneration. A very recent study demonstrated a pluripotent cytoprotective effect and mechanisms of HNs in cells not from the CNS, such as germ cells or pancreatic beta-cells, and the potent physiological consequences that result from FIN interaction with IGFBP3 and STAT3. In vivo studies suggest that HN may also protect against cognitive impairment due to ischemia/reperfusion injury.