Promising drugs to treat Alzheimers disease——?-secretase inhibitors
- VernacularTitle:AD治疗新药物——?-分泌酶抑制剂
- Author:
Hengwei XU
;
Lan SUN
;
Guanhua DU
;
- Publication Type:Journal Article
- Keywords:
Alzheimers disease;
? secretase;
presenlin;
? secretase inhibitor
- From:
Chinese Pharmacological Bulletin
2003;0(09):-
- CountryChina
- Language:Chinese
-
Abstract:
Mutations in presenilins caused most of the autosomal dominant familial forms of Alzheimers disease by altering ? secretase activity. The ? secretase is a large multiprotein complex including presenilin heterodimers,nicastrin,PEN 2 and additional unidentified components.? secretase cleaves beta amyloid precursor protein,Notch,E cadherin,ErbB 4 receptor tyrosine kinase and other membrane proteins.The development of various ? secretase inhibitors not only provides a tool for investigating the structure, function and mechanism of ? secretase,but also presents a therapeutic strategy to slow progression of Alzheimers disease pathology. Threre are various classes of ? secretase inhibitors: compounds containing a difluoro ketone or a difluoro alcohol group, (hydroxyethy) urea peptidomimetics,compounds possessing a hydroxyethylene dipeptide isostere, short helical peptides, non peptidic inhibitors derived from 4 chloro isocoumarin synthon, compounds containing alanyl moiety.Among these species of ? secretase inhibitors,those which selectively affect Abeta production are especially the most promising drugs to treat Alzheimers disease.
