title: Developing β-secretase inhibitors for treatment of Alzheimer's disease.
abstract: β-Secretase (memapsin 2; BACE-1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid-β (Aβ) in the brain. It is believed that high levels of brain Aβ are responsible for the pathogenesis of Alzheimer's disease (AD). Therefore, β-secretase is a major therapeutic target for the development of inhibitor drugs. During the past decade, steady progress has been made in the evolution of β-secretase inhibitors toward better drug properties. Recent inhibitors are potent, selective and have been shown to penetrate the blood-brain barrier to inhibit Aβ levels in the brains of experimental animals. Moreover, continuous administration of a β-secretase inhibitor was shown to rescue age-related cognitive decline in transgenic AD mice. A small number of β-secretase inhibitors have also entered early phase clinical trials. These developments offer some optimism for the clinical development of a disease-modifying drug for AD.
authors: Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana, USA.
authors: Arun K
authors: AK
authors: Ghosh
authors: Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana, USA.
authors: Margherita
authors: M
authors: Brindisi
authors: Protein Studies Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA.
authors: Jordan
authors: J
authors: Tang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D006801:Humans; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases