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P1‐438: The role of palmitoylation and farnesylation in the activation of β‐secretase and the release of amyloid‐β
Author(s) -
Ly Lucy,
Parsons Richard B.,
Austen Brian M.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1020
Subject(s) - palmitoylation , prenylation , cerulenin , chemistry , hek 293 cells , amyloid precursor protein secretase , biochemistry , amyloid precursor protein , brefeldin a , microbiology and biotechnology , golgi apparatus , cysteine , biology , cell , alzheimer's disease , enzyme , receptor , medicine , disease , pathology , fatty acid synthase
component (NAC) in brains of APP Tg mice. Methods: The mice of drug treated group were administered introgastrically by ICA (at doses 18 and 58 mg/kg/d) from 4 to 10 months old. The mice of normal group and negative transgene group were administered of distilled water by the same way. The learning-memory ability as measured by applying Morris water maze (MWM). The expression of APP, -secretase (BACE), and the expression of -synuclein in brains were detected by immunohistochemistry and western blot respectively. The content of amyloid 1-42 (A 1-42) were measured by ELISA Assay. The amyloid senile plaques were detected by Congo red staining. Results: The results showed that the escape latency and swimming distance in MWM of APP Tg mice were prolonged. The expression of APP, BACE, the content of A 1-42 decreased, the amount of amyloid senile plaques and the expression of -synuclein increased in brains of APP Tg mice. ICA decreased the latency and swimming distance in MWM test, decreased the expression of APP, BACE in both hippocampus and cortex and the content of A 1-42 in hippocampus of model mice, and relieved amyloid plaques burden in brains of model mice. Meanwhile, ICA suppressed the expression of synuclein. Conclusions: These results suggest that APP Tg mice could mimic pathological proceedings of AD. Icarrin may have a promising application prospect in treatment of AD.