| Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 96 === Beta amyloid (Abeta1-40), containing Abeta 25-35 as its toxic peptide, is the major component of Alzheimer's disease (AD) cortical senile plaques. It has been documented that some cases of AD are associated with peripheral abnormalities, including alterations in platelet function as well as Abeta deposition in the vessel occlusion with platelet accumulation. In addition, in vitro data also showed that Abeta possessing a fibrillar structure can trap platelet and results in platelet activation, which may induce a lot of diseases, such as atherosclerosis and thrombosis. This phenomenon was confirmed in this study by using human platelet aggregation assay. This study wants to resolve the action mechanism of Abeta 25-35 in platelet aggregation. In the study of microglia, phosphorylation of Vav and the multi-receptor cell surface complex consisted of CD36, alpha6beta1 integrin, CD47 and class A scavenger receptor are essential for intracellular signaling pathway leading to cell activation by fibrillar Abeta (fAbeta). This study of isolating human platelets represents a mechanism linking between fAbeta cell surface receptor complex, downstream Lyn and Syk kinases, phosphorylation of Vav, activation of PI3K and the downstream signaling events responsible for aggregation by Abeta 25-35. The current data show that the cell surface receptor complex consisted of scavenger receptor-A, downstream of Lyn and Syk kinases, PI3K , PLC, PKC engaged in platelet aggregation and calcium mobilization. Besides, Src and Syk inhibitors can reduce phosphrylation of Vav indicating that Vav is downstream protein regulated by class A scavenger receptor. In conclusion, platelet aggregation induced by Abeta 25-35�nmay be via class A scavenger receptor/ Src and Syk kinases/PI3K/Vav and PLC signaling pathway.
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