Effects of a DJ-1-Binding Compound on Spatial Learning and Memory Impairment in a Mouse Model of Alzheimer's Disease.
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.
Pharmacology and Neurobiology Laboratory, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan.|Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
Yoshihisa
Y
Kitamura
Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan.
Masatoshi
M
Inden
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
Yasuto
Y
Kimoto
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
Kazuyuki
K
Takata
Molecular Neuroscience Research Center, Shiga University of Medical Science, Shiga, Japan.
Daijiro
D
Yanagisawa
Pharmacology and Neurobiology Laboratory, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan.
Masanori
M
Hijioka
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
Eishi
E
Ashihara
Molecular Neuroscience Research Center, Shiga University of Medical Science, Shiga, Japan.
Ikuo
I
Tooyama
Department of Neurology, Sapporo Medical University, Sapporo, Japan.
Shun
S
Shimohama
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Hiroyoshi
H
Ariga
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology*; D004195:Disease Models, Animal; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008822:Mice, Transgenic; D018697:Nootropic Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1 / Q000378:metabolism; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
D016229:Amyloid beta-Peptides; D001549:Benzamides; D052117:Benzodioxoles; D018697:Nootropic Agents; D010446:Peptide Fragments; C540764:UCP0054278; C075222:amyloid beta-protein (1-42); C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1
Alzheimer’s disease; DJ-1; Parkinson’s disease; amyloid-β