The α- to γ-enolase switch : the role and regulation of γ-enolase during oligodendrocyte differentiation

Horvat, Selena (author), Pečar Fonović, Urša (author), Mitrović, Ana (author), Zidar, Nace (author), Kos, Janko (author), Pišlar, Anja (author)

The glycolytic enzyme γ-enolase is a highly specific neuronal marker that is known to replace ubiquitously expressed α-enolase in the brain. Moreover, γ-enolase has been shown to exert neurotrophic activity, which is regulated by cathepsin X, a lysosomal peptidase. This study investigates the role of γ-enolase and its regulation by cathepsin X during the differentiation of oligodendrocytes, which are essential for normal brain function. We established a differentiation protocol for the human oligodendroglioma (HOG) cell line and demonstrated for the first time that an α- to γ-enolase switch occurs during HOG cell differentiation. This switch was confirmed by the expression of specific markers underscoring the role of γ-enolase in oligodendrocyte differentiation. Moreover, γ-enolase overexpression enhanced oligodendrocyte differentiation, while silencing of γ-enolase by siRNA significantly decreased maturation marker. Further, the regulatory role of cysteine peptidase cathepsin X on γ-enolase function was found. Silencing cathepsin X significantly changed cell morphology, enhanced oligodendrocyte differentiation, altered the expression of oligodendrocyte markers, and increased levels of the active form of γ-enolase. Inhibiting cathepsin X similarly changed cell morphology and enhanced oligodendrocyte differentiation. These findings suggest that cathepsin X modulates γ-enolase activity and thereby influences oligodendrocyte differentiation and thus neuronal function.

• Language: English
• Keywords: oligodendrocytes, differentiation, γ-enolase, α-enolase, cathepsin X
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 15 str.
• Numbering: Vol. 301, art. 140464
• PID: 20.500.12556/RUL-167011
• UDC: 579
• ISSN on article: 1879-0003
• DOI: 10.1016/j.ijbiomac.2025.140464
• COBISS.SI-ID: 224856579
• Publication date in RUL: 03.02.2025

Record is a part of a journal

• Title: International journal of biological macromolecules
• Shortened title: Int. j. biol. macromol.
• Publisher: Elsevier
• ISSN: 1879-0003
• COBISS.SI-ID: 107163139

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: oligodendrociti, diferenciacija, γ-enolaza, α-enolaza, katepsin X

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P4-0127
• Name: Farmacevtska biotehnologija: znanost za zdravje