Stereochemistry of Sphingolipids in Ganglioside GM3 Enhances Recovery of Nervous Functionality

Sajeer Koolath; Yuta Murai; Tomoya Suzuki; Mahadeva M M Swamy; Seigo Usuki; Kenji Monde

doi:10.1021/acsmedchemlett.3c00252

Stereochemistry of Sphingolipids in Ganglioside GM3 Enhances Recovery of Nervous Functionality

ACS Med Chem Lett. 2023 Aug 14;14(9):1237-1241. doi: 10.1021/acsmedchemlett.3c00252. eCollection 2023 Sep 14.

Authors

Sajeer Koolath¹, Yuta Murai^{1

2

3}, Tomoya Suzuki¹, Mahadeva M M Swamy^{1

2}, Seigo Usuki⁴, Kenji Monde^{1

2}

Affiliations

¹ Graduate School of Life Science, Hokkaido University, Kita 21, Nishi 11, Sapporo 001-0021, Japan.
² Faculty of Advanced Life Science, Hokkaido University, Kita 21, Nishi 11, Sapporo 001-0021, Japan.
³ Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita 9, Nishi 9, Sapporo 060-8589, Japan.
⁴ Lipid Biofunction Section, Frontier Research Center for Advanced Material and Life Science, Faculty of Advanced Life Science, Hokkaido University, Kita 21, Nishi 11, Sapporo 001-0021, Japan.

PMID: 37736188
PMCID: PMC10510522 (available on 2024-09-14)
DOI: 10.1021/acsmedchemlett.3c00252

Abstract

GM3 is a simple monosialylated ganglioside (NeuAcα(2-3)Galβ(1-4)Glcβ1-1'-ceramide). Its aberrant expression in adipocytes is involved in a variety of physiological and pathological processes in diabetes mellitus and obesity. GM3 is exposed on the outer surface of cell membranes and is strongly associated with type 2 diabetes and insulin resistance. Exogenously added GM3 promotes neurite outgrowth in a variety of different neuroblastoma cell lines. Neurite outgrowth is a key process in the development of functional neuronal circuits and neuro-regeneration following nerve injury. Therefore, regulating GM3 levels in nerve tissues might be a potential treatment method for these disorders. Here, we demonstrate the comprehensive synthesis of stereoisomeric GM3s and compare their physicochemical properties with those of natural GM3 and diastereomers of sphingolipids in GM3 to examine the enhancement of biological activity. l-erythro-GM3 was confirmed to increase neurite outgrowth, providing valuable insights for potential neuro-regenerative treatments.