KRICT-9 inhibits neuroinflammation, amyloidogenesis and memory loss in Alzheimer’s disease models
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Do Yeon Lee1, Chul Ju Hwang1, Ji Yeon Choi1, Mi Hee Park1, Min Ji Song1, Ki Wan Oh1, Sang Bae Han1, Woo Kyu Park2, Hee Yeong Cho2, Sung Yun Cho2, Hye Byn Park2, Min Jong Song3 and Jin Tae Hong1
1College of Pharmacy and Medical Research Center, Chungbuk National University, Heungduk-gu, Chungbuk 361-951, Republic of Korea
2Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 34114, Republic of Korea
3Department of Obstetrics and Gynecology, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Jung-gu, Daejeon 301-723, Republic of Korea
Jin Tae Hong, email: firstname.lastname@example.org
Keywords: Alzheimer’s disease, STAT3, neuroinflammation, amyloidogenesis, KRICT-9
Received: January 09, 2017 Accepted: June 24, 2017 Published: August 02, 2017
Alzheimer’s disease (AD) is one of the most common forms of dementia and is characterized by neuroinflammation and amyloidogenesis. Here we investigated the effects of KRICT-9 on neuroinflammation and amyloidogenesis in in vitro and in vivo AD models. We found that KRICT-9 decreased lipopolysaccharide (LPS)-induced inflammation in microglial BV-2 cells and astrocytes while reducing nitric oxide generation and expression of inflammatory marker proteins (iNOS and COX-2) as well as APP, BACE1, C99, Iba-1, and GFAP. KRICT-9 also inhibited β-secretase. Pull-down assays and docking model analyses indicated that KRICT-9 binds to the DNA binding domain of signal transducer and activator of transcription 3 (STAT3). KRICT-9 also decreased β-secretase activity and Aβ levels in tissues from LPS-induced mice brains, and it reversed memory impairment in mice. These experiments demonstrated that KRICT-9 protects against LPS-induced neuroinflammation and amyloidogenesis by inhibiting STAT3 activity. This suggests KRICT-9 or KRICT-9-inspired reagents could be used as therapeutic agents to treat AD.
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