The sea urchin embryo: a model to study Alzheimer's beta amyloid induced toxicity.
Alzheimer's disease (AD) is the most common form of dementia. The cause of AD is closely related to the accumulation of amyloid beta peptide in the neuritic plaques. The use of animal model systems represents a good strategy to elucidate the molecular mechanism behind the development of this pathology. Here we use the Paracentrotus lividus embryo to identify molecules and pathways that can be involved in the degenerative process. As a first step, we identified the presence of an antigen related to the human APP, called PlAPP. This antigen, after gastrula stage, is processed producing a polypeptide of about 10kDa. By immunohistochemistry we localized the PlAPP antigen in some serotonin expressing cells. Similarly, after 48 or 96h incubation, a recombinant beta-amyloid peptide, rAbeta42, accumulates around the intestinal tube and oesophagus. In addition, incubation of sea urchin embryos with two different solutions rich in oligomers and fibrillar aggregates of rAbeta42 induce activation of apoptosis as detected by TUNEL assay. Moreover, we demonstrate that aggregates induce apoptosis by extrinsic pathway activation, whereas oligomers induce apoptosis both by extrinsic and intrinsic pathway activation. Utilizing an apoptotic inhibitor, caspases activation was offset and morphological damage rescued. Taken together all these observations suggest that the sea urchin may be a simple and suitable model to characterize the mechanism underlining the cytotoxicity of Abeta42.
Pellicanò
M
M
Istituto di Biomedicina ed Immunologia Molecolare, CNR, Palermo, Italy.
Picone
P
P
Cavalieri
V
V
Carrotta
R
R
Spinelli
G
G
Di Carlo
M
M
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D006801:Humans; D023421:Models, Animal; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D047328:Paracentrotus / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D011994:Recombinant Proteins / Q000378:metabolism / Q000633:toxicity
D016229:Amyloid beta-Peptides; D000941:Antigens; D010446:Peptide Fragments; D011994:Recombinant Proteins; C075222:amyloid beta-protein (1-42); D020169:Caspases