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P1‐151: Effect of targeting i 2 pp‐2a with sirnas on alzheimer‐like pathology in tg2576 mice
Author(s) -
Wei Wei
Publication year - 2009
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.2009.04.157
Subject(s) - hippocampus , hyperphosphorylation , phosphorylation , morris water navigation task , phosphatase , small interfering rna , chemistry , medicine , alzheimer's disease , cortex (anatomy) , immunohistochemistry , endocrinology , neuroscience , psychology , disease , biochemistry , rna , gene
the role of proteasome in the proteolysis of Ab is still uncertain. To explore the role of proteasome in Ab accumulation of AD pathologies, we investigated here the influence of proteasome inhibition on Ab production and the underlying mechanisms in rats. Methods: We injected bilaterally lactacystin, an irreversible inhibitor of proteasome, into the rat hippocampus and employed Western blotting, immunohistochemistry, and enzyme linked immunosorbent assay (ELISA) to measure the alterations of Ab production and the possible mechanisms in rats. Results: We observed the following results in our experiment. (1) Lactacystin inhibited the proteasome activities; (2) After proteasome inhibition, the level of Ab40 and Ab42 were both increased by ELISA, and Ab fragments were also increased by Wesstern blotting and immunohistochemstry with 4G8 and 6E10; (3) APP levels including full length and C-Terminal fragment cleaved by b-secretase (CTF-b) were elevated upon proteasome inhibition; (4) BACE1, PS-1 and PS-2 were increased at the different time points, witch suggested that b-secretase and g-secretase activity were increased after proteasome inhibition. Conclusions: We conclude that proteasome inhibition led to the increase of Ab production through elevating APP level and the band g-secretase activities in rat brain.