Spinosin Attenuates Alzheimer’s Disease-Associated Synaptic Dysfunction via Regulation of Plasmin Activity
Mudan Cai1,†, Inho Jung1,†, Huiyoung Kwon2, Eunbi Cho2, Jieun Jeon2, Jeanho Yun3,4, Young Choon Lee2,4, Dong Hyun Kim2,4,* and Jong Hoon Ryu1,5,*
1Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 02447,
2Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315,
3Department of Biochemistry, College of Medicine, Dong-A University, Busan 49201,
4Institute of Convergence Bio-Health, Dong-A University, Busan 49315,
5Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea
E-mail: jhryu63@khu.ac.kr (Ryu JH), mose79@dau.ac.kr (Kim DH)
Tel: +82-2-961-9230 (Ryu JH), +82-51-200-7583 (Kim DH)
Fax: +82-2-961-9580 (Ryu JH), +82-51-200-5748 (Kim DH)
The first two authors contributed equally to this work.
Received: May 3, 2019; Revised: August 27, 2019; Accepted: November 7, 2019; Published online: December 3, 2019.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Hippocampal synaptic dysfunction is a hallmark of Alzheimer’s disease (AD). Many agents regulating hippocampal synaptic plasticity show an ameliorative effect on AD pathology, making them potential candidates for AD therapy. In the present study, we investigated spinosin as a regulating agent of synaptic plasticity in AD. Spinosin attenuated amyloid β (Aβ)-induced long-term potentiation (LTP) impairment, and improved plasmin activity and protein level in the hippocampi of 5XFAD mice, a transgenic AD mouse model. Moreover, the effect of spinosin on hippocampal LTP in 5XFAD mice was prevented by 6-aminocaproic acid, a plasmin inhibitor. These results suggest that spinosin improves synaptic function in the AD hippocampus by regulating plasmin activity.
Keywords: Spinosin, Alzheimer’s disease, Plasmin, LTP, 5XFAD


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