Development of therapeutic strategy for intractable neuropsychiatric disease using chemical chaperones

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(1) Congo red inhibited the aggregate formation of mutant ・PKC, which caused spinocerebellar ataxia type 14 (SCA14), thereby, the cytotoxicity of SCA14 mutant ・PKC was reduced.(2) It is believed that 30 % of proteins are degraded by the chaperone-mediated autophagy (CMA). We developed the fluorescent-based probe, HaloTag-fused GAPDH, which can evaluate the cellular activity of CMA in single cell level. Using this probe, we demonstrated that CMA is inhibited in cells expressing SCA14 mutant ・PKC.(3) We revealed that 4-phenylbutylate (4-PBA), a chemical chaperone, increased the serotonin uptake activity of serotonin transporter (SERT) probably by accelerating SERT membrane trafficking.