Pub Date : 2010-07-06DOI: 10.2174/1874196701003010053
L. López, D. Acuña-Castroviejo, A. D. Pino, Miguel A. Tejada, G. Escames
{"title":"Mitochondrial Disorders Therapy: The Utility of Melatonin~!2009-11-18~!2010-01-21~!2010-06-23~!","authors":"L. López, D. Acuña-Castroviejo, A. D. Pino, Miguel A. Tejada, G. Escames","doi":"10.2174/1874196701003010053","DOIUrl":"https://doi.org/10.2174/1874196701003010053","url":null,"abstract":"","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76633041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-06-23DOI: 10.2174/18741967010030100053
L. López, D. Acuña-Castroviejo, A. D. Pino, Miguel A. Tejada, G. Escames
Mitochondria play a central role in the cell physiology. It is now recognized that, besides their classic function of energy metabolism, mitochondria are enrolled in multiple cell functions including energy distribution through the cell, energy/heat modulation, reactive oxygen species (ROS) regulation, calcium homeostasis, and apoptosis control. Recently, evidence is accumulating for a direct participation of mitochondria in stem cell proliferation and/or differentiation. All these functions suggest that mutations in either nuclear or mitochondrial DNA may induce serious cell impairments, and there is now evidence of more than 200 mtDNA mutations responsible for human pathologies. Moreover, mitochondria are, simultaneously, the main producer and target of ROS and, thus, multiple mitochondrial diseases are related to ROS- induced mitochondrial injuries. Among these, neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), inflammatory diseases such as sepsis, and aging itself, are caused or accompanied by ROS-induced mitochondrial dysfunctions. With regard to its action spectrum as an antioxidant, melatonin may be regarded as a first- choice agent for preventing and/or reducing the excess of ROS, thereby maintaining mitochondrial homeostasis. Multiple in vitro and in vivo experiments have shown the protective role of melatonin on mitochondrial physiology, yielding a significant improvement in those diseases in which energy supply to the cell had been compromised. New lines of evidence suggest the participation of mitochondria in stem cell proliferation and differentiation, and preliminary data support the role of melatonin in these processes. This review accounts for the multiple functions of mitochondria and the mechanisms involved in the numerous beneficial effects of melatonin to maintain mitochondrial homeostasis.
{"title":"Mitochondrial Disorders Therapy: The Utility of Melatonin","authors":"L. López, D. Acuña-Castroviejo, A. D. Pino, Miguel A. Tejada, G. Escames","doi":"10.2174/18741967010030100053","DOIUrl":"https://doi.org/10.2174/18741967010030100053","url":null,"abstract":"Mitochondria play a central role in the cell physiology. It is now recognized that, besides their classic function of energy metabolism, mitochondria are enrolled in multiple cell functions including energy distribution through the cell, energy/heat modulation, reactive oxygen species (ROS) regulation, calcium homeostasis, and apoptosis control. Recently, evidence is accumulating for a direct participation of mitochondria in stem cell proliferation and/or differentiation. All these functions suggest that mutations in either nuclear or mitochondrial DNA may induce serious cell impairments, and there is now evidence of more than 200 mtDNA mutations responsible for human pathologies. Moreover, mitochondria are, simultaneously, the main producer and target of ROS and, thus, multiple mitochondrial diseases are related to ROS- induced mitochondrial injuries. Among these, neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), inflammatory diseases such as sepsis, and aging itself, are caused or accompanied by ROS-induced mitochondrial dysfunctions. With regard to its action spectrum as an antioxidant, melatonin may be regarded as a first- choice agent for preventing and/or reducing the excess of ROS, thereby maintaining mitochondrial homeostasis. Multiple in vitro and in vivo experiments have shown the protective role of melatonin on mitochondrial physiology, yielding a significant improvement in those diseases in which energy supply to the cell had been compromised. New lines of evidence suggest the participation of mitochondria in stem cell proliferation and differentiation, and preliminary data support the role of melatonin in these processes. This review accounts for the multiple functions of mitochondria and the mechanisms involved in the numerous beneficial effects of melatonin to maintain mitochondrial homeostasis.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87554159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-05-04DOI: 10.2174/1874196701003010039
R. Hardeland, A. Coto-Montes
{"title":"New Vistas on Oxidative Damage and Aging~!2009-08-18~!2009-11-25~!2010-04-21~!","authors":"R. Hardeland, A. Coto-Montes","doi":"10.2174/1874196701003010039","DOIUrl":"https://doi.org/10.2174/1874196701003010039","url":null,"abstract":"","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86833933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-21DOI: 10.2174/18741967010030100039
R. Hardeland, A. Coto-Montes
Age-associated rises in oxidative damage are assumed to be a central phenomenon of aging. Their attenuation is an aim for both healthy aging and life extension. This review intends to critically discuss the potential of anti-oxidant actions, but even more to direct the attention to the modes of radical avoidance and to regulatory networks involved. Mitochondria seem to play a decisive role in radical formation and cellular decline. Avoidance and repair of disruptions in the electron transport chain reduce electron leakage and, thus, oxidative damage. Several low molecular weight compounds, such as melatonin, its metabolite N 1 -acetyl-5-methoxykynuramine, resveratrol, � -lipoic acid, and various mitochondrially targeted nitrones are capable of supporting mitochondrial electron flux. Some of them have been successfully used for extending the lifespan of experimental animals. Importantly, chemopreventive effects of these substances against cancer development should not be confused with a slowing of the aging process. We also focus on connections between these compounds and mitochondrial biogenesis, including the roles of sirtuins and signaling via peroxisome proliferator-activated receptor-� coactivator-1� , the participation of the circadian oscillator system in radical avoidance, as well as the potentially beneficial or detrimental effects of NO, as either a regulator or a source of mitochondrial dysfunction. Especially in the central nervous system, anti-excitatory actions by melatonin, kynurenic acid and theanine are discussed, which seem to prevent calcium overload that results in mitochondrial dysfunction. New findings on direct binding of melatonin to the amphipathic ramp of Complex I may indicate an additional regulatory role in the avoidance of electron leakage.
{"title":"New Vistas on Oxidative Damage and Aging","authors":"R. Hardeland, A. Coto-Montes","doi":"10.2174/18741967010030100039","DOIUrl":"https://doi.org/10.2174/18741967010030100039","url":null,"abstract":"Age-associated rises in oxidative damage are assumed to be a central phenomenon of aging. Their attenuation is an aim for both healthy aging and life extension. This review intends to critically discuss the potential of anti-oxidant actions, but even more to direct the attention to the modes of radical avoidance and to regulatory networks involved. Mitochondria seem to play a decisive role in radical formation and cellular decline. Avoidance and repair of disruptions in the electron transport chain reduce electron leakage and, thus, oxidative damage. Several low molecular weight compounds, such as melatonin, its metabolite N 1 -acetyl-5-methoxykynuramine, resveratrol, � -lipoic acid, and various mitochondrially targeted nitrones are capable of supporting mitochondrial electron flux. Some of them have been successfully used for extending the lifespan of experimental animals. Importantly, chemopreventive effects of these substances against cancer development should not be confused with a slowing of the aging process. We also focus on connections between these compounds and mitochondrial biogenesis, including the roles of sirtuins and signaling via peroxisome proliferator-activated receptor-� coactivator-1� , the participation of the circadian oscillator system in radical avoidance, as well as the potentially beneficial or detrimental effects of NO, as either a regulator or a source of mitochondrial dysfunction. Especially in the central nervous system, anti-excitatory actions by melatonin, kynurenic acid and theanine are discussed, which seem to prevent calcium overload that results in mitochondrial dysfunction. New findings on direct binding of melatonin to the amphipathic ramp of Complex I may indicate an additional regulatory role in the avoidance of electron leakage.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82826600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-07DOI: 10.2174/1874196701003020016
W. Araki
{"title":"β- and γ-Secretases and Lipid Rafts~!2009-08-25~!2010-01-18~!2010-03-19~!","authors":"W. Araki","doi":"10.2174/1874196701003020016","DOIUrl":"https://doi.org/10.2174/1874196701003020016","url":null,"abstract":"","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73248331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-07DOI: 10.2174/1874196701003020032
G. Eckert
{"title":"Manipulation of Lipid Rafts in Neuronal Cells~!2009-09-18~!2009-12-16~!2010-03-19~!","authors":"G. Eckert","doi":"10.2174/1874196701003020032","DOIUrl":"https://doi.org/10.2174/1874196701003020032","url":null,"abstract":"","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85693131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-07DOI: 10.2174/1874196701003020021
M. Lakshmana, Subhojit Roy, Kaihong Mi, D. Kang
{"title":"Amyloidogenic Processing of APP in Lipid Rafts~!2009-08-28~!2009-09-28~!2010-03-19~!","authors":"M. Lakshmana, Subhojit Roy, Kaihong Mi, D. Kang","doi":"10.2174/1874196701003020021","DOIUrl":"https://doi.org/10.2174/1874196701003020021","url":null,"abstract":"","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74699885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-03-19DOI: 10.2174/18741967010030100021
M. Lakshmana, Subhojit Roy, Kaihong Mi, D. Kang
Increased generation of amyloidpeptide (A� ) derived from amyloid precursor protein (APP) is the primary pathological characteristic of Alzheimer's disease (AD). However, the sub cellular compartment in which APP undergoes cleavage by secretases to generate A is not precisely known. Compelling evidences suggest that amyloidogenic processing of APP occurs in lipid rafts. An indirect support for lipid raft processing of APP includes the localization of A , APP C-terminal fragments (CTFs), APP holoprotein and secretases in the lipid raft microdomains, although few studies failed to find APP in the lipid rafts. The indirect support also comes from both experimental and clinical studies involving modulation of cholesterol levels and its effect on A generation. Moderate depletion of cholesterol results in significant reduction in A levels and increased dietary intake of cholesterol leads to higher levels of A production suggesting that amyloidogenic processing of APP strongly depends on cholesterol levels and therefore on lipid raft integrity. More convincing evidence that lipid rafts are critical for amyloidogenic processing of APP comes from studies using antibody-mediated co-patching of APP and BACE1 which results in lipid raft association of APP and BACE1 and increased A generation. Further, an endosome/lipid raft targeting of -secretase inhibitor by sterol-mediated anchoring leading to reduced A generation also suggests that lipid rafts are pivotal for amyloidogenic processing of APP. In the absence of an effective therapy for AD, proteins responsible for delivery of APP to lipid rafts including LRP, RanBP9 and ApoER2 may be excellent therapeutic targets in AD.
{"title":"Amyloidogenic Processing of APP in Lipid Rafts","authors":"M. Lakshmana, Subhojit Roy, Kaihong Mi, D. Kang","doi":"10.2174/18741967010030100021","DOIUrl":"https://doi.org/10.2174/18741967010030100021","url":null,"abstract":"Increased generation of amyloidpeptide (A� ) derived from amyloid precursor protein (APP) is the primary pathological characteristic of Alzheimer's disease (AD). However, the sub cellular compartment in which APP undergoes cleavage by secretases to generate A is not precisely known. Compelling evidences suggest that amyloidogenic processing of APP occurs in lipid rafts. An indirect support for lipid raft processing of APP includes the localization of A , APP C-terminal fragments (CTFs), APP holoprotein and secretases in the lipid raft microdomains, although few studies failed to find APP in the lipid rafts. The indirect support also comes from both experimental and clinical studies involving modulation of cholesterol levels and its effect on A generation. Moderate depletion of cholesterol results in significant reduction in A levels and increased dietary intake of cholesterol leads to higher levels of A production suggesting that amyloidogenic processing of APP strongly depends on cholesterol levels and therefore on lipid raft integrity. More convincing evidence that lipid rafts are critical for amyloidogenic processing of APP comes from studies using antibody-mediated co-patching of APP and BACE1 which results in lipid raft association of APP and BACE1 and increased A generation. Further, an endosome/lipid raft targeting of -secretase inhibitor by sterol-mediated anchoring leading to reduced A generation also suggests that lipid rafts are pivotal for amyloidogenic processing of APP. In the absence of an effective therapy for AD, proteins responsible for delivery of APP to lipid rafts including LRP, RanBP9 and ApoER2 may be excellent therapeutic targets in AD.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89368276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-03-19DOI: 10.2174/18741967010030100016
W. Araki
The cerebral accumulation of -amyloid protein (A ) is thought to play a key role in the molecular pathology of Alzheimer's disease (AD). Recent evidence indicates that both -secretase and -secretase, the membrane-associated proteases directly involved in the generation of A from its precursor, amyloid precursor protein (APP), are localized to cholesterol-rich membrane microdomains termed lipid rafts. This underscores the significance of lipid rafts in the amyloidogenic processing of APP. In the present mini-review, I summarize recent research developments that shed light on the association of -secretase and -secretase with lipid rafts, and discuss their implications for the pathology and therapeutics of AD.
{"title":"β- and γ-Secretases and Lipid Rafts","authors":"W. Araki","doi":"10.2174/18741967010030100016","DOIUrl":"https://doi.org/10.2174/18741967010030100016","url":null,"abstract":"The cerebral accumulation of -amyloid protein (A ) is thought to play a key role in the molecular pathology of Alzheimer's disease (AD). Recent evidence indicates that both -secretase and -secretase, the membrane-associated proteases directly involved in the generation of A from its precursor, amyloid precursor protein (APP), are localized to cholesterol-rich membrane microdomains termed lipid rafts. This underscores the significance of lipid rafts in the amyloidogenic processing of APP. In the present mini-review, I summarize recent research developments that shed light on the association of -secretase and -secretase with lipid rafts, and discuss their implications for the pathology and therapeutics of AD.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75122089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-03-19DOI: 10.2174/18741967010030100015
W. Araki
{"title":"Editorial: Lipid Rafts and Amyloidogenesis","authors":"W. Araki","doi":"10.2174/18741967010030100015","DOIUrl":"https://doi.org/10.2174/18741967010030100015","url":null,"abstract":"","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78376960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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