Developing β-secretase inhibitors for treatment of Alzheimer's disease

J. Neurochem. (2012) 120 (Suppl. 1), 71–83. 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...

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Bibliographic Details
Published in:Journal of neurochemistry 2012-01, Vol.120 (s1), p.71-83
Main Authors: Ghosh, Arun K., Brindisi, Margherita, Tang, Jordan
Format: Article
Language:English
Subjects:
Alzheimer Disease - drug therapy
Alzheimer Disease - enzymology
Alzheimer's disease
Amyloid precursor protein
Amyloid Precursor Protein Secretases - antagonists & inhibitors
Amyloid Precursor Protein Secretases - metabolism
Animals
BACE 1
beta-secretase
Blood-brain barrier
Brain
Clinical trials
Cognitive ability
Drug Delivery Systems - methods
Drug Delivery Systems - trends
Drug development
drugs
Humans
Inhibitors
memapsin 2
Neurodegenerative diseases
Pathogenesis
Protease Inhibitors - chemical synthesis
Protease Inhibitors - pharmacology
Protease Inhibitors - therapeutic use
Secretase
Therapeutic targets
Transgenic mice
Treatment Outcome
β-Site APP-cleaving enzymes
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Summary:J. Neurochem. (2012) 120 (Suppl. 1), 71–83. 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.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2011.07476.x