Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage

Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease that causes disability in patients. Cladribine is an oral treatment that is used in relapsing-remitting and active secondary progressive MS. T and B lymphocytes are especially sensitive to cladribine, which are transien...

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Autores: Eixarch, Herena|||0000-0001-7525-9533, Calvo-Barreiro, Laura|||0000-0002-8524-3305, Fissolo, Nicolás|||0000-0002-7701-9346, Boschert, Ursula, Hervera Abad, Arnau|||0000-0001-8362-369X, Comabella López, Manuel|||0000-0002-2373-6657, Montalban, Xavier|||0000-0002-0098-9918, Espejo, Carmen|||0000-0001-9949-5901
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:dnet:uabarcelona_::b844a2ba50b835eb82d7431decbc3b14
Acceso en línea:https://ddd.uab.cat/record/327814
https://dx.doi.org/urn:doi:10.3390/ijms262311311
Access Level:acceso abierto
Palabra clave:Cladribine
Multiple sclerosis
Disease modifying treatment
Central nervous system
Immunomodulation
Neuroprotection
Neurodegeneration
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spelling Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress DamageEixarch, Herena|||0000-0001-7525-9533Calvo-Barreiro, Laura|||0000-0002-8524-3305Fissolo, Nicolás|||0000-0002-7701-9346Boschert, UrsulaHervera Abad, Arnau|||0000-0001-8362-369XComabella López, Manuel|||0000-0002-2373-6657Montalban, Xavier|||0000-0002-0098-9918Espejo, Carmen|||0000-0001-9949-5901CladribineMultiple sclerosisDisease modifying treatmentCentral nervous systemImmunomodulationNeuroprotectionNeurodegenerationMultiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease that causes disability in patients. Cladribine is an oral treatment that is used in relapsing-remitting and active secondary progressive MS. T and B lymphocytes are especially sensitive to cladribine, which are transiently depleted upon short treatment courses. However, cladribine crosses the blood-brain barrier (BBB), supporting the hypothesis that cladribine may affect central nervous system (CNS)-resident cells. In this study, we used human primary cells and human cell lines to test the effect of cladribine, at therapeutic concentrations, on cells of the CNS. In these conditions, cladribine did not affect survival, proliferation and the capacity of producing cytokines of human microglial cells (HMC3 cell line) or primary human astrocytes but enhanced the production of oxygen reactive species in both cell types. The initial differentiation of primary human neuronal progenitor cells was impaired when continuously exposed to the maximum therapeutic concentration of cladribine, but not when lower concentrations were used. However, cladribine protected differentiated SH-SY5Y human neuroblastoma cell line from oxidative stress-related cell death. In conclusion, using different in vitro cell models, we demonstrate that cladribine maintains the normal function of CNS glia and protects neuronal cells from oxidative stress damage. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/327814https://dx.doi.org/urn:doi:10.3390/ijms262311311reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:uabarcelona_::b844a2ba50b835eb82d7431decbc3b142026-06-06T12:50:31Z
dc.title.none.fl_str_mv Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage
title Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage
spellingShingle Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage
Eixarch, Herena|||0000-0001-7525-9533
Cladribine
Multiple sclerosis
Disease modifying treatment
Central nervous system
Immunomodulation
Neuroprotection
Neurodegeneration
title_short Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage
title_full Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage
title_fullStr Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage
title_full_unstemmed Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage
title_sort Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage
dc.creator.none.fl_str_mv Eixarch, Herena|||0000-0001-7525-9533
Calvo-Barreiro, Laura|||0000-0002-8524-3305
Fissolo, Nicolás|||0000-0002-7701-9346
Boschert, Ursula
Hervera Abad, Arnau|||0000-0001-8362-369X
Comabella López, Manuel|||0000-0002-2373-6657
Montalban, Xavier|||0000-0002-0098-9918
Espejo, Carmen|||0000-0001-9949-5901
author Eixarch, Herena|||0000-0001-7525-9533
author_facet Eixarch, Herena|||0000-0001-7525-9533
Calvo-Barreiro, Laura|||0000-0002-8524-3305
Fissolo, Nicolás|||0000-0002-7701-9346
Boschert, Ursula
Hervera Abad, Arnau|||0000-0001-8362-369X
Comabella López, Manuel|||0000-0002-2373-6657
Montalban, Xavier|||0000-0002-0098-9918
Espejo, Carmen|||0000-0001-9949-5901
author_role author
author2 Calvo-Barreiro, Laura|||0000-0002-8524-3305
Fissolo, Nicolás|||0000-0002-7701-9346
Boschert, Ursula
Hervera Abad, Arnau|||0000-0001-8362-369X
Comabella López, Manuel|||0000-0002-2373-6657
Montalban, Xavier|||0000-0002-0098-9918
Espejo, Carmen|||0000-0001-9949-5901
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cladribine
Multiple sclerosis
Disease modifying treatment
Central nervous system
Immunomodulation
Neuroprotection
Neurodegeneration
topic Cladribine
Multiple sclerosis
Disease modifying treatment
Central nervous system
Immunomodulation
Neuroprotection
Neurodegeneration
description Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease that causes disability in patients. Cladribine is an oral treatment that is used in relapsing-remitting and active secondary progressive MS. T and B lymphocytes are especially sensitive to cladribine, which are transiently depleted upon short treatment courses. However, cladribine crosses the blood-brain barrier (BBB), supporting the hypothesis that cladribine may affect central nervous system (CNS)-resident cells. In this study, we used human primary cells and human cell lines to test the effect of cladribine, at therapeutic concentrations, on cells of the CNS. In these conditions, cladribine did not affect survival, proliferation and the capacity of producing cytokines of human microglial cells (HMC3 cell line) or primary human astrocytes but enhanced the production of oxygen reactive species in both cell types. The initial differentiation of primary human neuronal progenitor cells was impaired when continuously exposed to the maximum therapeutic concentration of cladribine, but not when lower concentrations were used. However, cladribine protected differentiated SH-SY5Y human neuroblastoma cell line from oxidative stress-related cell death. In conclusion, using different in vitro cell models, we demonstrate that cladribine maintains the normal function of CNS glia and protects neuronal cells from oxidative stress damage.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/327814
https://dx.doi.org/urn:doi:10.3390/ijms262311311
url https://ddd.uab.cat/record/327814
https://dx.doi.org/urn:doi:10.3390/ijms262311311
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
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