Study on Aβ34 biology and detection in transgenic mice brains.
The β-amyloid precursor protein undergoes cleavages by β- and γ-secretasses yielding amyloid-β peptides (Aβ) that accumulate in Alzheimer's disease. Subsequently, Aβ peptides are targets of additional truncations or endoproteolytic cleavages explaining the diversity of Aβ-related fragments recovered in cell media or pathologic human fluids. Here, we focused on Aβ1-34 (Aβ34) that has been detected both in vitro and in vivo and that derives from the hydrolysis of Aβ by β-secretase. We have obtained and fully characterized by immunologic and biochemical approaches, a polyclonal antibody that specifically recognizes the C-terminus of Aβx-34. We present immunohistochemical evidence for the presence of Aβx-34 in the brain of 3xTg mice and Alzheimer's disease-affected human brains. Finally, we demonstrate a neprilysin-mediated degradation process of Aβ34 and the ability of synthetic Aβ34 to protect HEK cells overexpressing either wild type or Swedish-mutated β-amyloid precursor protein from apoptosis.
Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 CNRS/UNS, Team "Fondation pour la Recherche Médicale" and "Labex Distalz", Valbonne, France.
Céline
C
Caillava
SysDiag CNRS-Bio-Rad, UMR3145, SysDiag,, Montpellier, France.
Sébastien
S
Ranaldi
Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 CNRS/UNS, Team "Fondation pour la Recherche Médicale" and "Labex Distalz", Valbonne, France.
Inger
I
Lauritzen
Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 CNRS/UNS, Team "Fondation pour la Recherche Médicale" and "Labex Distalz", Valbonne, France.
Charlotte
C
Bauer
SysDiag CNRS-Bio-Rad, UMR3145, SysDiag,, Montpellier, France.
Jeannette
J
Fareh
SysDiag CNRS-Bio-Rad, UMR3145, SysDiag,, Montpellier, France.
Jean-Daniel
JD
Abraham
Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 CNRS/UNS, Team "Fondation pour la Recherche Médicale" and "Labex Distalz", Valbonne, France. Electronic address: checler@ipmc.cnrs.fr.
Frédéric
F
Checler
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015260:Neprilysin / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C444321:amyloid beta-protein (1-34); D053829:Amyloid Precursor Protein Secretases; D053148:Caspase 3; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D015260:Neprilysin
3xTg mice; Alzheimer's disease; Apoptosis; Aβ34; Degradation; HEK cells; Human brain; Neprilysin; Polyclonal