Mechanism of protein phosphatase-2Aregulating phosphorylation of amyloid precursor proteosome and Aβ generation.

OBJECTIVE To discuss whether PP-2A influences the phosphorylation level at APP threonine 668 locus thus regulating Aβ secretion. METHOD In the experiment, 24 hours after N2a cells of stably transfected human APP (N2a/APP) were treated with okadaic acid (OA) or DES (C6-ceramide) (N2a/APP), an injection of OA cerebral stereotactic was administered to a SD rat in the hippocampal region, or PP-2A overexpressed plasmids was transfected transiently, the aggregate levels of APP phosphorylated APP, and APP-CTF were detected through immunoblotting and the activity of PP-2A and secretase was also detected using a reagent kit. RESULT The phosphorylation level of APP was significantly increased after the PP-2A activity was inhibited by OA. DES activated PP-2A or over-expressed PP-2A was able to reduce the phosphorylation level of APP. Either can inhibit PP and reduce the phosphorylation level of APP. The level of phosphorylated APP was increased significantly after the SD rat was injected with OA through the hippocampal region. The activity of β- and γ-secretases in N2a/APP cells significantly increased after OA treatment whereas the α-secretase activity had no significant changes; the Aβ level increased. CONCLUSION We discovered that PP-2A was capable of regulating the Aβ level by regulating APP phosphorylation level and β and γ-secretase activity(Fig. 5, Ref. 30).