Title:
【発明の名称】神経障害および神経変性疾患の治療のための組成物および方法
Document Type and Number:
Japanese Patent JP2003513917
Kind Code:
A
Abstract:
It has been discovered that the stimulation of betaadrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, or forskolin is inhibited by immunosuppressants, immunophilin ligands, or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium/calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.
Inventors:
Lee Robert Kay. Kay.
Bultmann Richard Jay.
Bultmann Richard Jay.
Application Number:
JP2001536138A
Publication Date:
April 15, 2003
Filing Date:
November 08, 2000
Export Citation:
Assignee:
Massachusetts Institute of Technology, Inc.
International Classes:
A61K31/00; A61K31/05; A61K31/137; A61K31/18; A61K31/198; A61K31/34; A61K31/365; A61K31/436; A61K31/465; A61K31/5383; A61K45/00; A61K31/5575; A61K38/13; A61K38/19; A61P9/00; A61P9/10; A61P25/00; A61P25/28; A61P29/00; A61P37/02; A61P43/00; (IPC1-7): A61K45/00; A61K31/05; A61K31/365; A61P9/00; A61P9/10; A61P25/00; A61P25/28; A61P29/00; A61P37/02; A61P43/00
Attorney, Agent or Firm:
Shimizu Hatsushi (1 person outside)