Glial cysteine cathepsins : from homeostasis to neurodegeneration

Suhadolc, Anja (avtor), Horvat, Selena (avtor), Kos, Janko (avtor), Pišlar, Anja (avtor)

Glial cells, namely microglia, astrocytes, and oligodendrocytes, play crucial roles in maintaining homeostasis in the central nervous system and orchestrating responses to injury, infection, and disease. Among the molecular regulators of glial function, cysteine cathepsins have emerged as key modulators of both physiological and pathological processes. These lysosomal peptidases are traditionally known for their housekeeping roles in protein degradation; however, accumulating evidence highlights their broader involvement in antigen presentation, microglial and astrocyte reactivity, inflammatory signalling, apoptosis, and myelination. Under normal conditions, cysteine cathepsins support essential functions in the central nervous system, including immune surveillance and tissue remodelling. Conversely, their dysregulation, characterized by overexpression, increased enzymatic activity, or mislocalization, can promote neuroinflammation and neurodegeneration, contributing to the pathogenesis of disorders such as Alzheimer’s disease and multiple sclerosis. This review provides a comprehensive synthesis specifically focused on the diverse roles of cysteine cathepsins across major glial cell types, systematically summarizing current knowledge in microglia, astrocytes, and oligodendrocytes. We emphasize their cell type-specific, context-dependent, protective, and deleterious functions. Furthermore, we discuss mechanistic links between cysteine cathepsin activity and neurodegenerative processes and evaluate the therapeutic potential and current limitations of selectively targeting glial cysteine cathepsins. A deeper understanding of the context-dependent dual roles of these enzymes in brain physiology and pathology is critical for designing targeted interventions that could mitigate neuroinflammation and neurodegeneration.

• Jezik: Angleški jezik
• Ključne besede: glial cells, neuroinflammation, neurodegeneration, cysteine cathepsins, therapeutic targets
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 24 str.
• Številčenje: Vol. 46, art. 146
• PID: 20.500.12556/RUL-189700
• UDK: 616.831-003.8
• ISSN pri članku: 1573-6830
• DOI: 10.1007/s10571-026-01776-w
• COBISS.SI-ID: 292874499
• Datum objave v RUL: 13.10.2026

Gradivo je del revije

• Naslov: Cellular and molecular neurobiology
• Skrajšan naslov: Cell. mol. neurobiol.
• Založnik: Kluwer
• ISSN: 1573-6830
• COBISS.SI-ID: 513133849

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: glialne celice, nevrovnetje, nevrodegeneracija, cisteinski katepsini, terapevtske tarče, nevrodegenerativne bolezni

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P4-0127
• Naslov: Farmacevtska biotehnologija: znanost za zdravje