Presenilin 1 (PS1), a causative molecule of familial Alzheimer's disease (AD), is known to be an unprimed substrate of glycogen synthase kinase 3 β (GSK3β) [Twomey and McCarthy (2006) FEBS Lett 580:4015-4020] and is phosphorylated at serine 353, 357 residues in its cytoplasmic loop region [Kirschenbaum et al. (2001) J Biol Chem 276:7366-7375]. In this report, we investigated the effect of PS1 phosphorylation on AD pathophysiology and obtained two important results--PS1 phosphorylation increased amyloid β (Aβ) 42/40 ratio, and PS1 phosphorylation was enhanced in the human AD brains. Interestingly, we demonstrated that PS1 phosphorylation promoted insulin receptor (IR) cleavage and the IR intracellular domain (IR ICD) generated by γ-secretase led to a marked transactivation of Akt (PKB), which down-regulated GSK3β activity. Thus, the cleavage of IR by γ-secretase can inhibit PS1 phosphorylation in the long run. Taken together, our findings indicate that PS1 phosphorylation at serine 353, 357 residues can play a pivotal role in the pathology of AD and that the dysregulation of this mechanism may be causally associated with its pathology.
Background: Premenstrual syndrome (PMS) causes physical and mental symptoms in women during the luteal phase of the menstruation cycle. To confirm the relationship between symptoms and the menstruation cycle, daily symptom records are essential for diagnosing PMS. The daily record of severity of problems (DRSP) is currently the most validated tool for tracking symptoms to confirm and scale the severity of PMS, but there has been no validated Japanese version of this instrument. We developed a Japanese version of the DRSP and assessed its psychometric properties. Methods: A Japanese version of the DRSP was developed following the translation guidelines of the latest Patient-Reported Outcomes Consortium. We conducted a computational psychometric study among 119 women, all of whom completed the Japanese version of the DRSP, the Center for Epidemiologic Studies Depression Scale (CES-D), the Premenstrual Dysphoric Disorder (PMDD) scale, and a Numerical Rating Scale (NRS) for general health status. Each was filled out twice, 2 weeks apart, so that one set was completed in the luteal phase. Results: The Japanese version of the DRSP was developed with translation and cultural adaptation. The internal consistency coefficient for the total score was 0.93. The DRSP in the luteal phase correlated highly with the CES-D, PMDD scale, and NRS for general health status. Conclusions: Our Japanese version of the DRSP, developed as a PMS/PMDD diagnostic tool, was shown to provide substantial validity and reliability to rate premenstrual symptoms for Japanese women.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.