[Strategies for identification of secretases implicated in Alzheimer's disease].
In Alzheimer's disease, cortical areas of affected patients are invaded by extracellular proteinous deposits called senile plaques, the main component of which is called amyloid beta-peptide or A beta. This peptide derives from the proteolytic attack of a precursor, the beta-amyloid precursor protein, by two enzymes called beta- and gamma-secretases. Alternatively, beta APP can be cleaved by an additional activity named alpha-secretase that occurs inside the A beta sequence, thereby precluding its formation, and concomitantly liberating a secreted fragment, namely APP alpha. Therefore, secretases seem to play a key role in the control of physiological and potentially pathogenic beta APP catabolites and could be envisioned as possible therapeutic targets in Alzheimer's disease. Here, we describe possible experimental approaches to identify such proteolytic activities.
Marambaud
P
P
IPMC du CNRS, UPR411, Valbonne, France.
Chevallier
N
N
Lopez-Perez
E
E
Drouot
C
C
Vizzanova
J
J
Fulcrand
P
P
Martinez
J
J
Wilk
S
S
Checler
F
F
D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases; D002402:Cathepsin D / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex
D016564:Amyloid beta-Protein Precursor; D009097:Multienzyme Complexes; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D002402:Cathepsin D; D046988:Proteasome Endopeptidase Complex