ABSTRACT
One of the pathological hallmarks of Alzheimer’s disease is the presence of insoluble extracellular amyloid plaques. These plaques are mainly constituted of amyloid beta peptide (Aβ), a proteolytic product of amyloid precursor protein (APP). APP processing also generates the APP intracellular domain (AICD). We have previously demonstrated that AICD interacts with FKBP12, a peptidyl-prolyl cis-trans isomerase (PPIase) ubiquitous in nerve systems. This interaction was interfered by FK506, a clinically used immunosuppressant that has recently been reported to be neuroprotective. To elucidate the roles of FKBP12 in the pathogenesis of Alzheimer’s disease, the effect of FKBP12 overexpression on APP processing was evaluated. Our results revealed that APP processing was shifted towards the amyloidogenic pathway, accompanied by a change in the subcellular localization of APP, upon FKBP12 overexpression. This FKBP12-overexpression-induced effect was reverted by FK506. These findings support our hypothesis that FKBP12 may participate in the regulation of APP processing. FKBP12 overexpression may lead to the stabilization of a certain isomer (presumably the cis form) of the Thr668-Pro669 peptide bond in AICD, therefore change its affinity to flotillin-1 or other raft-associated proteins, and eventually change the localization pattern and cause a shift in the proteolytic processing of APP.
ABSTRACT
[Objective] To explore the effects of the traditional Chinese drugs Chaiyuwendantang(CYWDT) and its component on the plasm levels of ACTH,COR and cAMP in hippocampus of depressed mode.[Methods] Eighty——four male rats were divided into seven groups: control group,depressed model group,group of CYWDT,group of HuaTan,group of TiaoQiXue,group of YangXinPi,group of maprotiline equally and made up models in chronic unpredictable mild stress(CUMS).The plasm levels of ACTH,COR and the level of cAMP in hippocampus were detected by radioimmunoassay.[Results] We found that the plasm levels of ACTH,COR were significantly increase and cAMP in hippocampus was significantly decreasd in depression model of rat.CYWDT and TiaoQiXue could significantly decreased the level of ACTH(P