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Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease
- Source :
- Medical Sciences, Vol 6, Iss 2, p 45 (2018), Medical Sciences
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- The present review analyzes the results of recent clinical trials of β secretase inhibition in sporadic Alzheimer’s disease (SAD), considers the striking dichotomy between successes in tests of β-site Amyloid Precursor Protein-Cleaving Enzyme (BACE) inhibitors in healthy subjects and familial Alzheimer’s disease (FAD) models versus persistent failures of clinical trials and interprets it as a confirmation of key predictions for a mechanism of amyloid precursor protein (APP)-independent, β secretase inhibition-resistant production of β amyloid in SAD, previously proposed by us. In light of this concept, FAD and SAD should be regarded as distinctly different diseases as far as β-amyloid generation mechanisms are concerned, and whereas β secretase inhibition would be neither applicable nor effective in the treatment of SAD, the β-site APP-Cleaving Enzyme (BACE) inhibitor(s) deemed failed in SAD trials could be perfectly suitable for the treatment of FAD. Moreover, targeting the aspects of Alzheimer’s disease (AD) other than cleavages of the APP by β and α secretases should have analogous impacts in both FAD and SAD.
- Subjects :
- 0301 basic medicine
Amyloid
lcsh:Medicine
amyloid precursor protein-independent generation of β amyloid
Review
amyloid precursor protein
sporadic Alzheimer’s disease
Disease
Pharmacology
β-site amyloid precursor protein-cleaving enzyme 1 inhibitors
03 medical and health sciences
0302 clinical medicine
mental disorders
familial Alzheimer’s disease
Amyloid precursor protein
Medicine
Beta (finance)
chemistry.chemical_classification
biology
business.industry
lcsh:R
Healthy subjects
Clinical trial
030104 developmental biology
Enzyme
chemistry
biology.protein
business
Alzheimer’s disease
Amyloid precursor protein secretase
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20763271
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Medical Sciences
- Accession number :
- edsair.doi.dedup.....30f0e7353d78847dce6427e7141cfa83