Neuronal subtype-specific expression of γ-enolase : its role in neuronal differentiation

Horvat, Selena (avtor), Pečar Fonović, Urša (avtor), Zidar, Nace (avtor), Doljak, Bojan (avtor), Kos, Janko (avtor), Pišlar, Anja (avtor)

Neuronal differentiation into specific subtypes is crucial for nervous system development and function, guided by neurotrophic factors. γ-Enolase, a neuron-specific glycolytic enzyme, exhibits neurotrophic-like properties and supports neuronal differentiation; however, its role in specific neuronal subtypes remains unknown. Here, we investigate the role of γ-enolase in differentiation dopaminergic-, cholinergic-, and adrenergic-like neuronal cells. Our results demonstrate that γ-enolase expression is significantly upregulated in differentiated cells, with the highest expression observed in cholinergic-like neurons. Full-length γ-enolase, compared to its truncated form, promoted enhanced neurite outgrowth and increased β-tubulin, a cytoskeletal marker. Conversely, silencing endogenous γ-enolase significantly reduced neurite length, confirming its essential role in driving neuronal morphological maturation. Furthermore, a γ-enolase-derived peptide corresponding to the active C-terminus of γ-enolase significantly promoted neurite outgrowth and increased β-tubulin expression, particularly in cholinergic-like neuronal cells. Notably, γ-enolase activity is regulated by cathepsin X, a lysosomal peptidase that cleaves γ-enolase at its C-terminus, reducing its neurotrophic effects. Confocal microscopy revealed increased co-localization of γ-enolase and cathepsin X in differentiated neuronal cells, emphasizing their interaction in cholinergic-like neurons. Inhibiting cathepsin X preserved active γ-enolase, promoted neuronal differentiation, and altered cytoskeletal marker expression. These findings suggest an important role for γ-enolase in cholinergic-like neuronal cells and propose cathepsin X as a regulatory modulator of γ-enolase activity, suggesting novel therapeutic strategies for neuroregeneration.

• Jezik: Angleški jezik
• Ključne besede: cathepsin x regulation, enolase isoforms, neuronal specific subtype, neurotrophic activity, γ-enolase
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 22 str.
• Številčenje: Vol. 28, iss. 1, art. 4
• PID: 20.500.12556/RUL-181041
• UDK: 577.152.34
• ISSN pri članku: 1559-1174
• DOI: 10.1007/s12017-025-08902-9
• COBISS.SI-ID: 272309507
• Datum objave v RUL: 23.03.2026

Gradivo je del revije

• Naslov: Neuromolecular medicine
• Skrajšan naslov: Neuromol. med.
• Založnik: Springer Nature
• ISSN: 1559-1174
• COBISS.SI-ID: 513713689

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: regulacija katepsina X, ozooblike enolaze, nevronsko specifični podtip, nevrotrofična aktivnost, γ-enolaza, katepsin X

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P4-0127
• Naslov: Farmacevtska biotehnologija: znanost za zdravje