Impact of sphingosine and acetylsphingosines on the aggregation and toxicity of metal-free and metal-treated amyloid-β.

Autor:	Yi Y; Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Republic of Korea miheelim@kaist.ac.kr., Lin Y; Research Center of Bioconvergence Analysis, Korea Basic Science Institute (KBSI) Ochang Chungbuk 28119 Republic of Korea mr0505@kbsi.re.kr., Han J; Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Republic of Korea miheelim@kaist.ac.kr., Lee HJ; Department of Chemistry Education, Kongju National University Gongju 32588 Republic of Korea., Park N; Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) Ulsan 44919 Republic of Korea., Nam G; Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) Ulsan 44919 Republic of Korea., Park YS; Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) Ulsan 44919 Republic of Korea., Lee YH; Research Center of Bioconvergence Analysis, Korea Basic Science Institute (KBSI) Ochang Chungbuk 28119 Republic of Korea mr0505@kbsi.re.kr.; Research Headquarters, Korea Brain Research Institute (KBRI) Daegu 41068 Republic of Korea.; Bio-Analytical Science, University of Science and Technology (UST) Daejeon 34113 Republic of Korea.; Graduate School of Analytical Science and Technology, Chungnam National University Daejeon 34134 Republic of Korea., Lim MH; Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Republic of Korea miheelim@kaist.ac.kr.
Jazyk:	angličtina
Zdroj:	Chemical science [Chem Sci] 2020 Dec 17; Vol. 12 (7), pp. 2456-2466. Date of Electronic Publication: 2020 Dec 17.
DOI:	10.1039/d0sc04366d
Abstrakt:	Pathophysiological shifts in the cerebral levels of sphingolipids in Alzheimer's disease (AD) patients suggest a link between sphingolipid metabolism and the disease pathology. Sphingosine ( SP ), a structural backbone of sphingolipids, is an amphiphilic molecule that is able to undergo aggregation into micelles and micellar aggregates. Considering its structural properties and cellular localization, we hypothesized that SP potentially interacts with amyloid-β (Aβ) and metal ions that are found as pathological components in AD-affected brains, with manifesting its reactivity towards metal-free Aβ and metal-bound Aβ (metal-Aβ). Herein, we report, for the first time , that SP is capable of interacting with both Aβ and metal ions and consequently affects the aggregation of metal-free Aβ and metal-Aβ. Moreover, incubation of SP with Aβ in the absence and presence of metal ions results in the aggravation of toxicity induced by metal-free Aβ and metal-Aβ in living cells. As the simplest acyl derivatives of SP , N -acetylsphingosine and 3- O -acetylsphingosine also influence metal-free Aβ and metal-Aβ aggregation to different degrees, compared to SP . Such slight structural modifications of SP neutralize its ability to exacerbate the cytotoxicity triggered by metal-free Aβ and metal-Aβ. Notably, the reactivity of SP and the acetylsphingosines towards metal-free Aβ and metal-Aβ is determined to be dependent on their formation of micelles and micellar aggregates. Our overall studies demonstrate that SP and its derivatives could directly interact with pathological factors in AD and modify their pathogenic properties at concentrations below and above critical aggregation concentrations. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu