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The visible light promoted, oxidative coupling of phenylhydrazine hydrochloride with 2H‐indazole derivatives has been demonstrated to obtain 3‐arylated‐2H‐indazole derivatives using a catalytic amount of 4CzIPN (1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene) as a photocatalyst under aerobic conditions. A library of arylated indazole derivatives was prepared in the organo‐photocatalytic pathway in good yields under mild reaction conditions. The present strategy was applied to synthesis liver X receptor agonist 4‐(7‐methoxy‐2‐phenyl‐2H‐indazol‐3‐yl) benzonitrile (3). [ABSTRACT FROM AUTHOR]

γ-Secretase is critically involved in the Notch pathway and in Alzheimer's disease. The four subunits of γ-secretase assemble in the endoplasmic reticulum (ER) and unassembled subunits are retained/retrieved to the ER by specific signals. We here describe a novel ER-retention/retrieval signal in the transmembrane domain (TMD) 4 of presenilin 1, a subunit of γ-secretase. TMD4 also is essential for complex formation, conferring a dual role for this domain. Likewise, TMD1 of Pen2 is bifunctional as well. It carries an ER-retention/retrieval signal and is important for complex assembly by binding to TMD4. The two TMDs directly interact with each other and mask their respective ER-retention/retrieval signals, allowing surface transport of reporter proteins. Our data suggest a model how assembly of Pen2 into the nascent γ-secretase complex could mask TMD-based ER-retention/retrieval signals to allow plasma membrane transport of fully assembled γ-secretase. [ABSTRACT FROM AUTHOR]