The chick embryo appears as a natural model for research in beta-amyloid precursor protein processing.
This study reveals that the chick embryo has active the machinery for the production and degradation of the amyloid beta peptide characteristic of Alzheimer's disease. We cloned the principal beta-amyloid precursor protein isoforms in the chick embryo and observed that they are highly homologous to the human sequences and identical at the C-terminal sequence, including the amyloid beta domain. Mammals such as rat or mouse, more commonly used as animal models of human diseases, have a distinct amyloid beta sequence. The distribution of beta-amyloid precursor protein isoforms in the chick embryo revealed that, as in humans, their expression is ubiquitous and the prototype beta-amyloid precursor protein-695 predominated in the nervous system. We also found that the chick embryo expresses the genes for the main proteolytic proteases implicated in the production of amyloid beta, including BACE-1, BACE-2, presenilin-1, presenilin-2 and nicastrin, as well as the amyloid beta-degrading enzyme neprilysin, or ADAM-17, a protease implicated in the non-amyloidogenic processing of beta-amyloid precursor protein. We have also found that between amyloid beta40 and amyloid beta42, this latter seems to be the major amyloid beta peptide produced during chick embryogenesis. The chick embryo appears as a suitable natural model to study cell biology and developmental function of beta-amyloid precursor protein and a potential assay system for drugs that regulate beta-amyloid precursor protein processing.
Carrodeguas
J A
JA
Laboratory of Neurobiology, Department of Anatomy, Embryology and Genetics, University of Zaragoza, Spain.
Rodolosse
A
A
Garza
M V
MV
Sanz-Clemente
A
A
Pérez-Pé
R
R
Lacosta
A M
AM
Domínguez
L
L
Monleón
I
I
Sánchez-Díaz
R
R
Sorribas
V
V
Sarasa
M
M
D000544:Alzheimer Disease / Q000503:physiopathology*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002642:Chick Embryo / Q000378:metabolism*; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D016564:Amyloid beta-Protein Precursor; D020033:Protein Isoforms; D010447:Peptide Hydrolases