# Lanthionine Ketimine Ethyl Ester Induces Proliferation and Maturation and Regulates Calcium Flux in Primary Mouse Oligodendrocyte Progenitor Cells

## TL;DR

LKE promotes the growth and maturation of oligodendrocyte progenitor cells and alters calcium signaling, which could help treat demyelinating diseases like multiple sclerosis.

## Contribution

This study reveals that LKE regulates calcium flux in OPCs and suggests CRMP2 as a key mediator of its effects.

## Key findings

- LKE increased OPC proliferation and maturation markers like Olig2+, CC1+, and PLP+.
- LKE reduced calcium influx in response to ATP and glutamate but increased it with KCl.
- A CRMP2-disrupting peptide produced similar calcium response effects as LKE.

## Abstract

Previous studies have shown that lanthionine ketimine ethyl ester (LKE), a semi‐synthetic derivative of the endogenous amino acid lanthionine, can induce proliferation and maturation of oligodendrocyte progenitor cells (OPCs) in vivo. In the current study, we examined the effects of LKE on Ca2+ influx in primary mouse OPCs, as intracellular Ca2+ can regulate those processes. Treatment with LKE stimulated proliferation of OPCs and increased the number of Olig2+, CC1+, and PLP+ cells. LKE also reduced cell death (caspase‐3 expressing cells). Measurements of Ca2+ flux showed that LKE increased basal Ca2+ levels, reduced Ca2+ influx following stimulation with glutamate or ATP, and increased Ca2+ flux because of depolarization with KCl. Reduced Ca2+ responses were also observed following treatment with a peptide that disrupts interactions of collapsin response mediated protein 2 (CRMP2), a primary target of LKE. These findings demonstrate regulation of Ca2+ levels in OPCs by LKE and suggest that these actions may be mediated, in part, by CRMP2. LKE or related analogs could therefore be of benefit for the treatment of multiple sclerosis as well as other demyelinating conditions.

LKE increased OPC proliferation and maturation. LKE reduced Ca responses to ATP and glutamate, and increased responses to KCl. Similar effects occurred with a peptide that disrupts Collapsin Response Mediator Protein 2 interactions with NMDARs and VGCCs.