@article{oai:repo.qst.go.jp:00075972,
 author = {Hashimoto, Shoko and Matsuba, Yukio and Kamano, Naoko and MIhira, Naomi and Sahara, Naruhiko and Takano, Jiro and Shin-ichi, Muramatsu and C. Saido, Takaomi and Saito, Takashi and Sahara, Naruhiko},
 issue = {1},
 journal = {Nature Communications},
 month = {Jun},
 note = {To understand the molecular processes that link Aβ amyloidosis, tauopathy and neurodegeneration, we screened for tau-interacting proteins by immunoprecipitation/LC-MS. We identified the carboxy-terminal PDZ ligand of nNOS (CAPON) as a novel tau-binding protein. CAPON is an adaptor protein of neuronal nitric oxide synthase (nNOS), and activated by the N-methyl-D-aspartate receptor. We observed accumulation of CAPON in the hippocampal pyramidal cell layer in the AppNL-G-F -knock-in (KI) brain. To investigate the effect of CAPON accumulation on Alzheimer’s disease (AD) pathogenesis, CAPON was overexpressed in the brain of AppNL-G-F mice crossbred with MAPT (human tau)-KI mice. This produced significant hippocampal atrophy and caspase3-dependent neuronal cell death in the CAPON-expressing hippocampus, suggesting that CAPON accumulation increases neurodegeneration. CAPON expression also induced significantly higher levels of phosphorylated, oligomerized and insoluble tau. In contrast, CAPON deficiency ameliorated the AD-related pathological phenotypes in tauopathy model. These findings suggest that CAPON could be a druggable AD target.},
 title = {Tau binding protein CAPON induces tau aggregation and neurodegeneration},
 volume = {10},
 year = {2019}
}