Humanin, a polypeptide suppressing neuronal death

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/09 (2006.01) A61K 38/10 (2006.01) A61K 38/17 (2006.01) A61K 48/00 (2006.01) A61P 25/00 (2006.01) A61P 25/28 (2006.01) C07K 7/08 (2006.01) C07K 14/47 (2006.01) C07K 16/18 (2006.01) C12N 1/15 (2006.01) C12N 1/19 (2006.01) C12N 1/21 (2006.01) C12N 5/10 (2006.01) C12P 21/02 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2385444

A polypeptide which inhibits nerve cell death in association with Alzheimer's disease. By using a nerve cell system capable of inducing the expression of familial Alzheimer's disease variant APP by treating with ecdysone, a gene having an activity of protecting the nerve cells from cell death is successfully isolated. This gene encodes a secretory polypeptide consisting of 24 amino acids. This polypeptide shows an activity of inhibiting nerve cell death caused by the expression of an APP variant and a presenilin variant. This polypeptide also inhibits cell death caused by A.beta. in primary nerve culture. By modifying the amino acids of this polypeptide, moreover, the cell death inhibitory activity can be significantly elevated. These polypeptides and derivatives thereof are useful as medicines for preventing nerve cell death in association with Alzheimer's disease and as seed compounds for developing novel medicines for Alzheimer's disease.

L'invention concerne un polypeptide qui inhibe la mort de cellules nerveuses relative à la maladie d'Alzheimer. Au moyen d'un système de cellules nerveuses capable d'induire l'expression d'un APP variant de la maladie d'Alzheimer par traitement avec l'ecdysone, un gène qui possède une activité de protection des cellules nerveuses de la mort cellulaire est isolé. Ce gène code un polypeptide sécrétoire comprenant 24 acides aminés. Ce polypeptide présente une activité d'inhibition de la mort des cellules nerveuses provoquée par l'expression d'un variant APP et d'un variant de préséniline. Ce polypeptide inhibe aussi la mort cellulaire occasionnée par A.beta. dans une culture nerveuse primaire. La modification des acides aminés de ce polypeptide permet d'augmenter de manière considérable l'activité inhibitrice de la mort cellulaire. Ces polypeptides et les dérivés correspondants sont utilisés en tant que médicaments de prévention de la mort de cellules nerveuses relative à la maladie d'Alzheimer et en tant que composés de grains de développement de nouveaux médicaments pour lutter contre la maladie d'Alzheimer.

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