Effects of a DJ-1-Binding Compound on Spatial Learning and Memory Impairment in a Mouse Model of Alzheimer’s Disease

Article type: Short Communication

Authors: Kitamura, Yoshihisa^{a; b; *} | Inden, Masatoshi^c | Kimoto, Yasuto^b | Takata, Kazuyuki^b | Yanagisawa, Daijiro^d | Hijioka, Masanori^a | Ashihara, Eishi^b | Tooyama, Ikuo^d | Shimohama, Shun^e | Ariga, Hiroyoshi^{f; *}

Affiliations: [a] Pharmacology and Neurobiology Laboratory, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan | [b] Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan | [c] Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan | [d] Molecular Neuroscience Research Center, Shiga University of Medical Science, Shiga, Japan | [e] Department of Neurology, Sapporo Medical University, Sapporo, Japan | [f] Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

Correspondence: [*] Correspondence to: Yoshihisa Kitamura, PhD, Pharmacology and Neurobiology Laboratory, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga 525-8577, Japan. Tel.: +81 77 561 5296; E-mail: [email protected] and Hiroyoshi Ariga, PhD, Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. Tel.: +81 11 706 3745; Fax: +81 11 706 4988; E-mail: [email protected].

Abstract: Previously, DJ-1 modulator UCP0054278/comp-B was identified by virtual screening, where comp-B interacts with DJ-1 to produce antioxidant and neuroprotective responses in Parkinson’s disease models. However, the effect of comp-B in an in vivo Alzheimer’s disease (AD) model is yet undetermined. Thus, we examined the effect of comp-B on spatial learning, memory, and amyloid-β (Aβ) clearance in a transgenic mouse model of AD. We found that comp-B resolved the cognitive deficits, reduced insoluble Aβ42 levels, and prevented the degeneration of synaptic functions, thereby suggesting that comp-B may become a major compound for AD treatment.

Keywords: Alzheimer’s disease, amyloid-β, DJ-1, Parkinson’s disease

DOI: 10.3233/JAD-160574

Journal: Journal of Alzheimer's Disease, vol. 55, no. 1, pp. 67-72, 2017