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. 2019 Dec 5;9:18393. doi: 10.1038/s41598-019-54846-z

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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YU102 improves cognitive impairment in a mouse model of inflammation induced by LPS (lipopolysaccharide). (a) Proteasome inhibitory activity of immunoproteasome (iP) inhibitors (YU102, PR-924), YU102 epimer (an inactive stereoisomer of YU102) and constitutive proteasome (cP) inhibitor (PR-825). Data is shown as mean ± SD derived from a non-linear regression based on n = 3 replicates per compound per concentration. ^aIC₅₀ values were determined from competition assays in Raji cell lysates⁸⁵. ^bIC₅₀ values were approximated from ProCISE assay using A20 murine lymphoma cells¹⁴. ^cIC50 values were obtained from ProCISE ELISA using MOLT-4 human leukemia cells⁸⁶. (b) A schematic depicting the experimental schedule for ICR mice. Dose of YU102 (10 mg/kg) was determined based on its in vitro potency relative to the in vitro potencies of carfilzomib and bortezomib for which effective doses were previously reported⁸⁷. (c) Spatial recognition memory was evaluated by the Morris water maze test: escape latency time in the target quadrant (above) and escape distance of the mice (below). Statistical analyses of escape latency and escape distance were performed via two-way ANOVA. *Differences in escape latency on days 4–6 and distance on day 6 between LPS-treated and YU102 treated were statistically significant (p-value < 0.05, n = 5).