The metabolism of amyloid β‐protein precursor (APP) is regulated by various cytoplasmic and/or membrane‐associated proteins, some of which are involved in the regulation of intracellular membrane trafficking. We found that a protein containing Asp–His–His–Cys (DHHC) domain, alcadein and APP interacting DHHC protein (AID)/DHHC‐12, strongly inhibited APP metabolism, including amyloid β‐protein (Aβ) generation. In cells expressing AID/DHHC‐12, APP was tethered in the Golgi, and APP‐containing vesicles disappeared from the cytoplasm. Although DHHC domain‐containing proteins are involved in protein palmitoylation, a AID/DHHC‐12 mutant of which the enzyme activity was impaired by replacing the DHHC sequence with Ala–Ala–His–Ser (AAHS) made no detectable difference in the generation and trafficking of APP‐containing vesicles in the cytoplasm or the metabolism of APP. Furthermore, the mutant AID/DHHC‐12 significantly increased non‐amyloidogenic α‐cleavage of APP along with activation of a disintegrin and metalloproteinase 17, a major α‐secretase, suggesting that protein palmitoylation involved in the regulation of α‐secretase activity. AID/DHHC‐12 can modify APP metabolism, including Aβ generation in multiple ways by regulating the generation and/or trafficking of APP‐containing vesicles from the Golgi and their entry into the late secretary pathway in an enzymatic activity‐independent manner, and the α‐cleavage of APP in the enzymatic activity‐dependent manner.
A pharmacopoeia's core mission is to protect public health by creating and making available public standards to help ensure the quality of drugs. In recent years, pharmacopoeias around the world have harmonized their standards in the present context of globalized drug supply chains and markets. For example, the Pharmacopoeial Discussion Group has worked to harmonize excipient monographs and general chapters. In addition, the International Meeting of World Pharmacopoeias has been held by the WHO to discuss information exchange and international collaboration, among other topics. To contribute further to the protection of public health in the globalized drug market, we conducted a comparative study of the pharmacopoeias in Japan, Europe, and the United States. We aimed to examine current differences among the Japanese Pharmacopoeia, the European Pharmacopoeia, and the United States Pharmacopeia-National Formulary and to identify areas that require further collaboration among the three pharmacopoeias. In this study, we analyzed monographs and general chapters listed in the three pharmacopoeias. We identified the features of the monographs and general chapters listed in each pharmacopoeia, as well as differences across the pharmacopoeias. Moreover, on the basis of our findings, we suggest standards that require further collaboration among the pharmacopoeias in certain preferred areas. The comparison data produced by this study are expected to be used to develop strategies for future revisions of pharmacopoeias around the world.
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