Melatonin and mitochondrial dysfunction in the central nervous system

Autores
Cardinali, Daniel Pedro; Pagano, Eleonora Samanta; Scacchi Bernasconi, Pablo Antonio; Reynoso, Roxana María; Scacchi, Pablo
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cell death and survival are critical events for neurodegeneration, mitochondria being increasingly seen as important determinants of both. Mitochondrial dysfunction is considered a major causative factor in Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity and NO production, and disrupted electron transport system and mitochondrial permeability transition, have all been involved in impaired mitochondrial function. Melatonin, the major secretory product of the pineal gland, is an antioxidant and an effective protector of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective to prevent oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of AD, PD and HD. These effects are seen at doses 2–3 orders of magnitude higher than those required to affect sleep and circadian rhythms, both conspicuous targets of melatonin action. Melatonin is selectively taken up by mitochondria, a function not shared by other antioxidants. A limited number of clinical studies indicate that melatonin can improve sleep and circadian rhythm disruption in PD and AD patients. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50–100 mg/day are needed to assess its therapeutic validity in neurodegenerative disorders.
Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pagano, Eleonora Samanta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
Fil: Scacchi Bernasconi, Pablo Antonio. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Reynoso, Roxana María. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
Fil: Scacchi, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
Materia
Melatonin
Mitochondria
Free radicals
Oxidative stress
Aging
Parkinson's disease
Huntington's disease
Melatonin analogs
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/271947
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/271947
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Melatonin and mitochondrial dysfunction in the central nervous systemCardinali, Daniel PedroPagano, Eleonora SamantaScacchi Bernasconi, Pablo AntonioReynoso, Roxana MaríaScacchi, PabloMelatoninMitochondriaFree radicalsOxidative stressAgingParkinson's diseaseHuntington's diseaseMelatonin analogshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Cell death and survival are critical events for neurodegeneration, mitochondria being increasingly seen as important determinants of both. Mitochondrial dysfunction is considered a major causative factor in Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity and NO production, and disrupted electron transport system and mitochondrial permeability transition, have all been involved in impaired mitochondrial function. Melatonin, the major secretory product of the pineal gland, is an antioxidant and an effective protector of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective to prevent oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of AD, PD and HD. These effects are seen at doses 2–3 orders of magnitude higher than those required to affect sleep and circadian rhythms, both conspicuous targets of melatonin action. Melatonin is selectively taken up by mitochondria, a function not shared by other antioxidants. A limited number of clinical studies indicate that melatonin can improve sleep and circadian rhythm disruption in PD and AD patients. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50–100 mg/day are needed to assess its therapeutic validity in neurodegenerative disorders.Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pagano, Eleonora Samanta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; ArgentinaFil: Scacchi Bernasconi, Pablo Antonio. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reynoso, Roxana María. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; ArgentinaFil: Scacchi, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; ArgentinaAcademic Press Inc Elsevier Science2013-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/271947Cardinali, Daniel Pedro; Pagano, Eleonora Samanta; Scacchi Bernasconi, Pablo Antonio; Reynoso, Roxana María; Scacchi, Pablo; Melatonin and mitochondrial dysfunction in the central nervous system; Academic Press Inc Elsevier Science; Hormones And Behavior; 63; 2; 2-2013; 322-3300018-506XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0018506X12000517info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yhbeh.2012.02.020info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:18:47Zoai:ri.conicet.gov.ar:11336/271947instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:18:47.56CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Melatonin and mitochondrial dysfunction in the central nervous system
title Melatonin and mitochondrial dysfunction in the central nervous system
spellingShingle Melatonin and mitochondrial dysfunction in the central nervous system
Cardinali, Daniel Pedro
Melatonin
Mitochondria
Free radicals
Oxidative stress
Aging
Parkinson's disease
Huntington's disease
Melatonin analogs
title_short Melatonin and mitochondrial dysfunction in the central nervous system
title_full Melatonin and mitochondrial dysfunction in the central nervous system
title_fullStr Melatonin and mitochondrial dysfunction in the central nervous system
title_full_unstemmed Melatonin and mitochondrial dysfunction in the central nervous system
title_sort Melatonin and mitochondrial dysfunction in the central nervous system
dc.creator.none.fl_str_mv Cardinali, Daniel Pedro
Pagano, Eleonora Samanta
Scacchi Bernasconi, Pablo Antonio
Reynoso, Roxana María
Scacchi, Pablo
author Cardinali, Daniel Pedro
author_facet Cardinali, Daniel Pedro
Pagano, Eleonora Samanta
Scacchi Bernasconi, Pablo Antonio
Reynoso, Roxana María
Scacchi, Pablo
author_role author
author2 Pagano, Eleonora Samanta
Scacchi Bernasconi, Pablo Antonio
Reynoso, Roxana María
Scacchi, Pablo
author2_role author
author
author
author
dc.subject.none.fl_str_mv Melatonin
Mitochondria
Free radicals
Oxidative stress
Aging
Parkinson's disease
Huntington's disease
Melatonin analogs
topic Melatonin
Mitochondria
Free radicals
Oxidative stress
Aging
Parkinson's disease
Huntington's disease
Melatonin analogs
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cell death and survival are critical events for neurodegeneration, mitochondria being increasingly seen as important determinants of both. Mitochondrial dysfunction is considered a major causative factor in Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity and NO production, and disrupted electron transport system and mitochondrial permeability transition, have all been involved in impaired mitochondrial function. Melatonin, the major secretory product of the pineal gland, is an antioxidant and an effective protector of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective to prevent oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of AD, PD and HD. These effects are seen at doses 2–3 orders of magnitude higher than those required to affect sleep and circadian rhythms, both conspicuous targets of melatonin action. Melatonin is selectively taken up by mitochondria, a function not shared by other antioxidants. A limited number of clinical studies indicate that melatonin can improve sleep and circadian rhythm disruption in PD and AD patients. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50–100 mg/day are needed to assess its therapeutic validity in neurodegenerative disorders.
Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pagano, Eleonora Samanta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
Fil: Scacchi Bernasconi, Pablo Antonio. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Reynoso, Roxana María. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
Fil: Scacchi, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
description Cell death and survival are critical events for neurodegeneration, mitochondria being increasingly seen as important determinants of both. Mitochondrial dysfunction is considered a major causative factor in Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity and NO production, and disrupted electron transport system and mitochondrial permeability transition, have all been involved in impaired mitochondrial function. Melatonin, the major secretory product of the pineal gland, is an antioxidant and an effective protector of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective to prevent oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of AD, PD and HD. These effects are seen at doses 2–3 orders of magnitude higher than those required to affect sleep and circadian rhythms, both conspicuous targets of melatonin action. Melatonin is selectively taken up by mitochondria, a function not shared by other antioxidants. A limited number of clinical studies indicate that melatonin can improve sleep and circadian rhythm disruption in PD and AD patients. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50–100 mg/day are needed to assess its therapeutic validity in neurodegenerative disorders.
publishDate 2013
dc.date.none.fl_str_mv 2013-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/271947
Cardinali, Daniel Pedro; Pagano, Eleonora Samanta; Scacchi Bernasconi, Pablo Antonio; Reynoso, Roxana María; Scacchi, Pablo; Melatonin and mitochondrial dysfunction in the central nervous system; Academic Press Inc Elsevier Science; Hormones And Behavior; 63; 2; 2-2013; 322-330
0018-506X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/271947
identifier_str_mv Cardinali, Daniel Pedro; Pagano, Eleonora Samanta; Scacchi Bernasconi, Pablo Antonio; Reynoso, Roxana María; Scacchi, Pablo; Melatonin and mitochondrial dysfunction in the central nervous system; Academic Press Inc Elsevier Science; Hormones And Behavior; 63; 2; 2-2013; 322-330
0018-506X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0018506X12000517
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yhbeh.2012.02.020
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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