Activities of curcumin-related compounds in two cell lines persistently infected with different prion strains

• Published in: Biochimica et biophysica acta. General subjects Vol. 1866; no. 4; p. 130094
• Main Authors: Teruya, Kenta, Iwabuchi, Sara, Watanabe, Yuki, Tsuchida, Rikiya, Watanabe-Matsui, Miki, Konno, Hiroyuki, Doh-ura, Katsumi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2022
• Subjects: Anti-prion; Cell Line; chemometrics; Curcumin; Curcumin - pharmacology; dose response; hydrogen; hydrophobicity; Partial least squares; Prion; Prion Proteins; prions; Prions - chemistry; Prions - metabolism; Protein cross-linking; PrPSc Proteins - metabolism; F_unbound; PrPres; PrPSc; LP; DMSO; CNS; SA; Anti-prion; PLS; IC50; Curcumin; Partial least squares; Protein cross-linking; PBS; Acceptor; SDS; VDss; IR; MW; Rot_Bond; CNS_p; PrP; BBB_p; PrPC; Donor; Prion; PK; N2a; ATR
• DOI: 10.1016/j.bbagen.2022.130094
• ISSN: 0304-4165; 1872-8006

Cultured cell lines infected with prions produce an abnormal isoform of the prion protein (PrPSc). In this study, two types of cells persistently infected with prion were treated with curcumin-related compounds. We found that the compounds behave differently in neuroblastoma neuro-2a (N2a) cells infected with different prion strains. Curcumin and related compounds were applied to the two types of persistently prion infected cells to analyze the different activities of the compounds. In ScN2a cells, which were infected with the Rocky Mountain Laboratory prion strain, two of the six compounds significantly reduced the PrPSc level in a dose-dependent manner. On the other hand, in N167 cells, effective suppression of the total amount of PrPSc was not observed; instead, two other compounds promoted the formation of covalently linked PrPSc dimers. Chemometric analysis was used to determine the factors that contributed to the different effects of the six compounds. It showed that the ability to form hydrogen bonds, such as phenolic hydroxyl groups, and hydrophobic molecular properties predominantly contributed to the reduction of the PrPSc level in the ScN2a cells and the dimer formation of PrPSc in the N167 cells, respectively. The extracted information can be used to delineate the differences among prion strains and to design compounds that are directed toward their respective activities. [Display omitted] •Two cells infected with different prion strains were treated with several compounds.•In one of the cells, the level of abnormal prion protein was reduced.•In the other cells, cross-linked dimer of abnormal prion protein was formed.•The different activities were explained with the characteristics of the compounds.•Preferable parameters for the respective activities of compounds were obtained.