Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice

Oxidative stress and neuroinflammation are major contributors to the pathophysiology of ALS. Nicotinamide riboside (a NAD + precursor) and pterostilbene (a natural antioxidant) were efficacious in a human pilot study of ALS patients and in ALS SOD1 G93A transgenic mice. Ibudilast targets different p...

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Autores: López-Blanch R, Salvador-Palmer R, Oriol-Caballo M, Moreno-Murciano P, Dellinger RW, Estrela JM, Obrador E
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:INCLIVA
Repositório:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p18066
Acesso em linha:https://incliva.portalinvestigacion.com/publicaciones/18066
Access Level:Acceso aberto
Palavra-chave:Amyotrophic lateral sclerosis
Motor neurons
Oxidative stress
Nitric oxide
Neuroinflammation
NAD plus
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spelling Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS miceLópez-Blanch RSalvador-Palmer ROriol-Caballo MMoreno-Murciano PDellinger RWEstrela JMObrador EAmyotrophic lateral sclerosisMotor neuronsOxidative stressNitric oxideNeuroinflammationNAD plusOxidative stress and neuroinflammation are major contributors to the pathophysiology of ALS. Nicotinamide riboside (a NAD + precursor) and pterostilbene (a natural antioxidant) were efficacious in a human pilot study of ALS patients and in ALS SOD1 G93A transgenic mice. Ibudilast targets different phosphodiesterases and the macrophage migration inhibitory factor, reduces neuroinflammation, and in early -phase studies improved survival and slowed progression in ALS patients. Using two ALS murine models (SOD1 G93A , FUS R521C ) the effects of nicotinamide riboside, pterostilbene, and ibudilast on disease onset, progression and survival were studied. In both models ibudilast enhanced the effects of nicotinamide riboside and pterostilbene on survival and neuromotor functions. The triple combination reduced microgliosis and astrogliosis, and the levels of different proinflammatory cytokines in the CSF. TNF alpha, IFN gamma and IL1 beta increased H 2 O 2 and NO generation by motor neurons, astrocytes, microglia and endothelial cells isolated from ALS mice. Nicotinamide riboside and pterostilbene decreased H 2 O 2 and NO generation in all these cells. Ibudilast specifically decreased TNF alpha levels and H 2 O 2 generation by microglia and endothelial cells. Unexpectedly, pathophysiological concentrations of H 2 O 2 or NO caused minimal motor neuron cytotoxicity. H 2 O 2 -induced cytotoxicity was increased by NO via a trace metal -dependent formation of potent oxidants (i.e. OH and - OONO radicals). In conclusion, our results show that the combination of nicotinamide riboside, pterostilbene and ibudilast improve neuromotor functions and survival in ALS murine models. Studies on the underlying mechanisms show that motor neuron protection involves the decrease of oxidative and nitrosative stress, the combination of which is highly damaging to motor neurons.ELSEVIER SCIENCE INC2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/18066NeurotherapeuticsISSN: 19337213ISSNe: 18787479reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p180662026-06-07T16:35:31Z
dc.title.none.fl_str_mv Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice
title Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice
spellingShingle Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice
López-Blanch R
Amyotrophic lateral sclerosis
Motor neurons
Oxidative stress
Nitric oxide
Neuroinflammation
NAD plus
title_short Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice
title_full Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice
title_fullStr Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice
title_full_unstemmed Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice
title_sort Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice
dc.creator.none.fl_str_mv López-Blanch R
Salvador-Palmer R
Oriol-Caballo M
Moreno-Murciano P
Dellinger RW
Estrela JM
Obrador E
author López-Blanch R
author_facet López-Blanch R
Salvador-Palmer R
Oriol-Caballo M
Moreno-Murciano P
Dellinger RW
Estrela JM
Obrador E
author_role author
author2 Salvador-Palmer R
Oriol-Caballo M
Moreno-Murciano P
Dellinger RW
Estrela JM
Obrador E
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Amyotrophic lateral sclerosis
Motor neurons
Oxidative stress
Nitric oxide
Neuroinflammation
NAD plus
topic Amyotrophic lateral sclerosis
Motor neurons
Oxidative stress
Nitric oxide
Neuroinflammation
NAD plus
description Oxidative stress and neuroinflammation are major contributors to the pathophysiology of ALS. Nicotinamide riboside (a NAD + precursor) and pterostilbene (a natural antioxidant) were efficacious in a human pilot study of ALS patients and in ALS SOD1 G93A transgenic mice. Ibudilast targets different phosphodiesterases and the macrophage migration inhibitory factor, reduces neuroinflammation, and in early -phase studies improved survival and slowed progression in ALS patients. Using two ALS murine models (SOD1 G93A , FUS R521C ) the effects of nicotinamide riboside, pterostilbene, and ibudilast on disease onset, progression and survival were studied. In both models ibudilast enhanced the effects of nicotinamide riboside and pterostilbene on survival and neuromotor functions. The triple combination reduced microgliosis and astrogliosis, and the levels of different proinflammatory cytokines in the CSF. TNF alpha, IFN gamma and IL1 beta increased H 2 O 2 and NO generation by motor neurons, astrocytes, microglia and endothelial cells isolated from ALS mice. Nicotinamide riboside and pterostilbene decreased H 2 O 2 and NO generation in all these cells. Ibudilast specifically decreased TNF alpha levels and H 2 O 2 generation by microglia and endothelial cells. Unexpectedly, pathophysiological concentrations of H 2 O 2 or NO caused minimal motor neuron cytotoxicity. H 2 O 2 -induced cytotoxicity was increased by NO via a trace metal -dependent formation of potent oxidants (i.e. OH and - OONO radicals). In conclusion, our results show that the combination of nicotinamide riboside, pterostilbene and ibudilast improve neuromotor functions and survival in ALS murine models. Studies on the underlying mechanisms show that motor neuron protection involves the decrease of oxidative and nitrosative stress, the combination of which is highly damaging to motor neurons.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/18066
url https://incliva.portalinvestigacion.com/publicaciones/18066
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER SCIENCE INC
publisher.none.fl_str_mv ELSEVIER SCIENCE INC
dc.source.none.fl_str_mv Neurotherapeutics
ISSN: 19337213
ISSNe: 18787479
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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