Alzheimer's disease is characterized at the histopathological level by neurofibrillary tangles, senile plaques and massive neuronal loss. Senile plaques are composed by the aggregation of amyloid-beta peptide., which is produced after cleavage of a transmembrane protein, betaAPP, by two enzymatic activities, named beta- and gamma-secretases....
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November 26, 2007 (v1)PublicationUploaded on: December 4, 2022
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October 5, 2018 (v1)Journal article
International audience
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2011 (v1)Journal article
Proteolytic degradation has emerged as a key pathway involved in controlling levels of the Alzheimer's disease (AD)-associated amyloid-β peptides (Aβ) in the brain. The ectopeptidase, neprilysin (NEP), has been reported as the major Aβ-degrading enzyme in mice and human brains. We have previously shown that NEP expression and activity are...
Uploaded on: December 3, 2022 -
2010 (v1)Journal article
Amyloid beta-peptides is the generic term for a set of hydrophobic peptides that accumulate in Alzheimer's disease (AD)-affected brains. These amyloid-beta peptide fragments are mainly generated by an enzymatic machinery referred to as gamma-secretase complex that is built up by the association of four distinct proteins, namely presenilin 1...
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April 2007 (v1)Journal article
The presenilin-dependent gamma-secretase activity, which is responsible for the generation of amyloid beta-peptide, is a high molecular weight complex composed of at least four components, namely, presenilin-1 (or presenilin-2), nicastrin, Aph-1, and Pen-2. Previous data indicated that presenilins, which are thought to harbor the catalytic core...
Uploaded on: February 28, 2023 -
June 2021 (v1)Journal article
One of the main components of senile plaques in Alzheimer's disease (AD)-affected brain is the Aβ peptide species harboring a pyroglutamate at position three pE3-Aβ. Several studies indicated that pE3-Aβ is toxic, prone to aggregation and serves as a seed of Aβ aggregation. The cyclisation of the glutamate residue is produced by glutaminyl...
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April 2009 (v1)Journal article
Nicastrin (NCT) is a component of the presenilin (PS)-dependent gamma-secretase complexes that liberate amyloid beta-peptides from the beta-Amyloid Precursor Protein. Several lines of evidence indicate that the members of these complexes could also contribute to the control of cell death. Here we show that over-expression of NCT increases the...
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May 25, 2018 (v1)Journal article
International audience
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June 20, 2008 (v1)Journal article
The presenilin (PS)-dependent gamma-secretase activity refers to a high molecular mass-complex including, besides PS1 or PS2, three other proteins recently identified, namely nicastrin, Aph-1, and Pen-2. This proteolytic complex has been shown to contribute to both gamma- and epsilon-cleavages of the beta-amyloid precursor protein (betaAPP),...
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2007 (v1)Journal article
The presenilin-dependent gamma-secretase complex is mainly composed of four distinct proteins, namely presenilin 1 or presenilin 2, nicastrin, anterior pharynx defective-1 (Aph-1) and presenilin enhancer (Pen-2). The mechanisms by which the complex is assembled, how its stoichiometry is controlled and how its catalytic activity is regulated are...
Uploaded on: February 28, 2023 -
February 2007 (v1)Journal article
International audience
Uploaded on: December 3, 2022 -
February 15, 2007 (v1)Journal article
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Uploaded on: February 28, 2023 -
November 1, 2009 (v1)Journal article
The senile plaques found in the brains of patients with Alzheimer's disease are mainly due to the accumulation of amyloid beta-peptides (A beta) that are liberated by gamma-secretase, a high molecular weight complex including presenilins, PEN-2, APH-1 and nicastrin. The depletion of each of these proteins disrupts the complex assembly into a...
Uploaded on: December 4, 2022 -
March 2018 (v1)Journal article
BACKGROUND: Mitophagy and mitochondrial dynamics alterations are two major hallmarks of neurodegenerative diseases. Dysfunctional mitochondria accumulate in Alzheimer's disease-affected brains by yet unexplained mechanisms. METHODS: We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway...
Uploaded on: December 4, 2022