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We identified a biomarker candidate for Pick’s disease using robust protein-unfolding activity, designated Unfoldin, which was purified from yeast cells. Unfoldin localized to the cell periphery at the stationary phase, whereas it was on the budding sites during the log phase and then surrounded the bud neck during cell division. ATP, but not its hydrolysis, promoted Unfoldin binding to protein substrates and unfolded their conformation. A total of 514 Pick bodies were purified and isolated with a laser-microdissection system without a healthy brain region and solubilized with Unfoldin in the presence of ATP, and then the components were analyzed using a shotgun protein analysis by liquid chromatography-tandem mass spectroscopy. A MASCOT analysis revealed that calmodulin-like skin protein is a possible marker protein for Pick’s disease, and it was localized in the Pick bodies of a patient with Pick’s disease. Unfoldin will open the way to diagnostics and therapeutics, particularly for protein-aggregation related diseases.

Calmodulin-Like Skin Protein (CLSP) is a Novel Biomarker Candidate for Pick’s Disease by Unfoldin-Modified Proteomic Analysis