Humanin, a novel gene encoding 24 amino acid polypeptide inhibits cell death by Alzheimers disease-related insults

By functional screening that called "death trap" with our modification, we identified a novel gene, designated Humanin (HN) cDNA, encoding a 24 amino acid polypeptide. which inhibited neuronal cell death by familial Alzheimers disease (FAD)-causal genes [V642I amyloid precursor protein (APP), K595N/M596L APP, M146L presenilin (PS)-1, and N141I PS- 2]. HN had no antagonistic effect on neuronal cell death by GAG repeats diseases-associated polyglutamine stretch Q79, familial amyotrophic lateral sclerosis-related SOD1 mutants, and etoposide. Transfected HN cDNA was transcribed to the corresponding polypeptide, and then was secreted into culture media, and acting on cells from the out side. Synthetic HN polypeptide showed antagonistic effect against amyloid β peptides in primary cultured neurons. These results indicate that this novel polypeptide provides the basis for the development of curative therapy for Alzheimers disease.