C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 7/08 (2006.01) A61K 38/08 (2006.01) A61K 38/10 (2006.01) C07K 7/06 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2097533
PEPTIDES HAVING NEUROPROTECTIVE AND IMMUNOSTIMULATORY FUNCTIONS ABSTRACT OF THE DISCLOSURE Histogranin having the structure Image and analogs thereof having NMDA and/or AMPA receptor agonist and/or antagonist activities both in vivo by their blockade of NMDA- and AMPA-induced convulsions and in vitro by their binding and allosteric interactions with domains of the NMDA receptor complex and their potentiation of host-defense immune responses (IL-l production and IL-1.alpha. mRNA induction in alveolar macrophages) are herein described. Histogranin is a natural compound which can be extracted from suitable tissue, e.g. bovine adrenal medulla, or synthesized using the solid- phase peptide synthesis procedure. Histogranin and specific active fragments and analogs are potent ligands of a specific receptor linked to the NMDA and/or AMPA receptors: they block NMDA- and AMPA-receptor stimulation and therefore can be considered as good protecting agents against nerve cell degeneration due to an overstimulation of the NMDA and/or AMPA receptors, an event observed in the following brain disturbances: ischaemia, stroke, epilepsy, Alzheimer's disease, spinal cord trauma, anxiety, schizophrenia and Huntington's disease. Some analogs are also proposed as putative antagonists of the histogranin receptor and therefore have potential beneficial use as enhancer of NMDA receptor stimulation, a process involved in learning and memory. In periphery, the ability of histogranin (and analogs) in enhancing the immune responses of immune cells such as alveolar macrophages stresses its potential use for the treatment of immune disorders (immunodeficiency related to AIDS, U.V. exposure or other immune disorders).
Kirby Eades Gale Baker
Lemaire Simon
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