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Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.
Overexpression of a transmembrane aspartic protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta- secretase positions.
Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease.
It is indicated that the FAD-linked mutations may all cause Alzhelmer's disease by increasing the extracellular concentration of A beta 42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide.
Control of Peripheral Nerve Myelination by the ß-Secretase BACE1
It is found that very high levels of BACE1 were expressed at time points when peripheral nerves become myelinated and correct bundling of axons by Schwann cells, probably through processing of type III NRG1.
Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice
The data demonstrate that the preseniiin mutations cause a dominant gain of function and may induce AD by enhancing Aβ42 production, thus promoting cerebral β-amyloidosis.
Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production
C cultured cells which express a β-APP complementary DNA bearing a double mutation found in a Swedish FAD family produce ∼6–8-fold more Aβ than cells expressing normalβ-APP, and this increase is confirmed for elucidating the fundamental mechanism of Alzheimer's disease.
Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production.
C cultured cells which express a beta-APP complementary DNA bearing a double mutation found in a Swedish FAD family produce approximately 6-8-fold more A beta than cells expressing normalbeta-APP, establishing a direct link between a FAD genotype and the clinicopathological phenotype.
Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease
The findings indicate that the FAD–linked mutations may all cause Alzheimer's disease by increasing the extracellular concentration of Aβ42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide.
Alzheimer's disease: strategies for disease modification
- M. Citron
- BiologyNature Reviews Drug Discovery
- 1 May 2010
Recent progress with strategies targeting the production and clearance of the amyloid-β peptide, a cardinal feature of Alzheimer's disease that is thought to be important in disease pathogenesis, are discussed.
Title beta-secretase cleavage of Alzheimer ' s amyloid precursor protein by the transmembrane aspartic protease
Strategies for disease modification in Alzheimer's disease
- M. Citron
- BiologyNature Reviews Neuroscience
- 1 September 2004
All three main classes of disease-modification approaches can be defined: one that is broadly neurotrophic or neuroprotective, one that targets specific aspects of AD pathology, and one that was based on epidemiological observation.