Lewis X-Carrying Neoglycolipids Evoke Selective Apoptosis in Neural Stem Cells

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2017 Oct 12

PMID 29019053

Authors

Hirokazu Yagi

Gengwei Yan

Tatsuya Suzuki

Shingo Tsuge

Takumi Yamaguchi

Koichi Kato

Affiliations

Soon will be listed here.

Abstract

N-glycans carrying the Lewis X trisaccharide [Galβ1-4 (Fucα1-3) GlcNAc] are expressed by neural stem cells (NSCs) exclusively before differentiation, and they actively contribute to the maintenance of stemness of these cells. To address the functional roles of the Lewis X-mediated molecular interactions in NSCs, we created a series of synthetic neoglycolipids that contained a Lewis X-carrying glycan connected to an acyl chain through an amide bond. The neoglycolipids formed aqueous micelles displaying functional Lewis X glycotopes. Surprisingly, the neoglycolipid micelles evoked selective apoptosis in undifferentiated NSCs, whereas their differentiated cells remained unaffected. The apoptotic activity depended on the structural integrity of the Lewis X glycotopes and also on the length of the acyl chain, with an optimum length of C18. We propose hypothetical functional mechanisms of the neoglycolipid, which involves selective NSC targeting with Lewis X glycan and apoptotic signaling by the intracellular release of fatty acids. This serendipitous finding may offer a new strategy for controlling neural cell fates using artificial glycoclusters.

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