Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease
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...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2018-06-01
|
Series: | Medical Sciences |
Subjects: | |
Online Access: | http://www.mdpi.com/2076-3271/6/2/45 |
id |
doaj-d12f8f4fca3d45218c73c0e49ce87cc9 |
---|---|
record_format |
Article |
spelling |
doaj-d12f8f4fca3d45218c73c0e49ce87cc92020-11-24T23:32:09ZengMDPI AGMedical Sciences2076-32712018-06-01624510.3390/medsci6020045medsci6020045Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s DiseaseVladimir Volloch0Sophia Rits1Deptartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USAHoward Hughes Medical Institute at Children’s Hospital, Boston, MA 02115, USAThe 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.http://www.mdpi.com/2076-3271/6/2/45Alzheimer’s diseaseamyloid precursor proteinfamilial Alzheimer’s diseasesporadic Alzheimer’s diseaseβ-site amyloid precursor protein-cleaving enzyme 1 inhibitorsamyloid precursor protein-independent generation of β amyloid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Vladimir Volloch Sophia Rits |
spellingShingle |
Vladimir Volloch Sophia Rits Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease Medical Sciences Alzheimer’s disease amyloid precursor protein familial Alzheimer’s disease sporadic Alzheimer’s disease β-site amyloid precursor protein-cleaving enzyme 1 inhibitors amyloid precursor protein-independent generation of β amyloid |
author_facet |
Vladimir Volloch Sophia Rits |
author_sort |
Vladimir Volloch |
title |
Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease |
title_short |
Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease |
title_full |
Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease |
title_fullStr |
Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease |
title_full_unstemmed |
Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease |
title_sort |
results of beta secretase-inhibitor clinical trials support amyloid precursor protein-independent generation of beta amyloid in sporadic alzheimer’s disease |
publisher |
MDPI AG |
series |
Medical Sciences |
issn |
2076-3271 |
publishDate |
2018-06-01 |
description |
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. |
topic |
Alzheimer’s disease amyloid precursor protein familial Alzheimer’s disease sporadic Alzheimer’s disease β-site amyloid precursor protein-cleaving enzyme 1 inhibitors amyloid precursor protein-independent generation of β amyloid |
url |
http://www.mdpi.com/2076-3271/6/2/45 |
work_keys_str_mv |
AT vladimirvolloch resultsofbetasecretaseinhibitorclinicaltrialssupportamyloidprecursorproteinindependentgenerationofbetaamyloidinsporadicalzheimersdisease AT sophiarits resultsofbetasecretaseinhibitorclinicaltrialssupportamyloidprecursorproteinindependentgenerationofbetaamyloidinsporadicalzheimersdisease |
_version_ |
1725535153389830144 |