Falla mitocondrial oxidativa inducida por estrés y sustancias vasoactivas como los iniciadores dominantes de la patología favorecen la reclasificación de la enfermedad de Alzheimer como una Vasocognopatía

Aliev, Gjumrakch; Lamanna, Joséph Charles; Morales Álvarez, Ludis; Obrenovich, Mark Eric; Pacheco, Gerardo Jesús; Palacios, Hector; Qasimov, Eldar; Walrafen, Brianna

dc.creator	Aliev, Gjumrakch
dc.creator	Lamanna, Joséph Charles
dc.creator	Morales Álvarez, Ludis
dc.creator	Obrenovich, Mark Eric
dc.creator	Pacheco, Gerardo Jesús
dc.creator	Palacios, Hector
dc.creator	Qasimov, Eldar
dc.creator	Walrafen, Brianna
dc.date	2008-12-15
dc.date.accessioned	2022-02-22T19:57:16Z
dc.date.available	2022-02-22T19:57:16Z
dc.identifier	https://hemeroteca.unad.edu.co/index.php/nova/article/view/408
dc.identifier	10.22490/24629448.408
dc.identifier.uri	https://repository.unad.edu.co/handle/10596/46703
dc.description	Alzheimer disease and cerebrovascular accident are two leading causes of age-related dementia. Increasing evidence supports the idea that chronic hypoperfusion is primarily responsible for the pathogenesis that underlies both disease processes. Hypoperfusion is associated with oxidative imbalance, largely due to reactive oxygen species, which is associated with other age-related degenerative disorders. Recent evidence indicates that a chronic injury stimulus induces the hypoperfusion seen in the microcirculation of vulnerable regions of the brain. This leads to energy failure, manifested by damaged mitochondrial ultrastructure. Mitochondrial derangements lead to the formation of a large number of electron-dense, “hypoxic” mitochondria and cause the overproduction of mitochondrial DNA (mtDNA) deletions, which is most likely due to double stranded breaks. Additionally, these mitochondrial abnormalities coexist with increased redox metal activity, lipid peroxidation, and RNA oxidation, all of which are well established features of Alzheimer disease pathology, prior to the appearance of amyloid b deposition.Alzheimer disease, oxidative stress occurs within various cellular compartments and within certain cell types more than others, namely the vascular endothelium, which is associated with atherosclerotic damage, as well as in pyramidal neurons and glia. Interestingly, these vulnerable cells show mtDNA deletions and oxidative stress markers only in the regions that are closely associated with damaged vessels. This evidence strongly suggests that chronic hypoperfusion induces the accumulation of the oxidative stress products. Furthermore, brain vascular wall lesions linearly correlate with the degree of neuronal and glial cell damage. We, therefore, conclude that chronic hypoperfusion is a key initiator of oxidative stress in various brain parenchymal cells, and the mitochondria appear to be primary targets for brain damage in Alzheimer disease. In this manuscript, we outline a role for the continuous accumulation of oxidative stress products, such as an abundance of nitric oxide products (via the overexpression of inducible and/or neuronal NO synthase (iNOS and nNOS respectively) and peroxynitrite accumulation, as secondary but accelerating factors compromising the blood brain barrier (BBB). If this turns out to be the case, pharmacological interventions that target chronic hypoperfusion might ameliorate the key features of dementing neurodegeneration.	en-US
dc.description	Alzheimer disease and cerebrovascular accident are two leading causes of age-related dementia. Increasing evidence supports the idea that chronic hypoperfusion is primarily responsible for the pathogenesis that underlies both disease processes. Hypoperfusion is associated with oxidative imbalance, largely due to reactive oxygen species, which is associated with other age-related degenerative disorders. Recent evidence indicates that a chronic injury stimulus induces the hypoperfusion seen in the microcirculation of vulnerable regions of the brain. This leads to energy failure, manifested by damaged mitochondrial ultrastructure. Mitochondrial derangements lead to the formation of a large number of electron-dense, ¿hypoxic¿ mitochondria and cause the overproduction of mitochondrial DNA (mtDNA) deletions, which is most likely due to double stranded breaks. Additionally, these mitochondrial abnormalities coexist with increased redox metal activity, lipid peroxidation, and RNA oxidation, all of which are well established features of Alzheimer disease pathology, prior to the appearance of amyloid b deposition. Alzheimer disease, oxidative stress occurs within various cellular compartments and within certain cell types more than others, namely the vascular endothelium, which is associated with atherosclerotic damage, as well as in pyramidal neurons and glia. Interestingly, these vulnerable cells show mtDNA deletions and oxidative stress markers only in the regions that are closely associated with damaged vessels. This evidence strongly suggests that chronic hypoperfusion induces the accumulation of the oxidative stress products. Furthermore, brain vascular wall lesions linearly correlate with the degree of neuronal and glial cell damage. We, therefore, conclude that chronic hypoperfusion is a key initiator of oxidative stress in various brain parenchymal cells, and the mitochondria appear to be primary targets for brain damage in Alzheimer disease. In this manuscript, we outline a role for the continuous accumulation of oxidative stress products, such as an abundance of nitric oxide products (via the overexpression of inducible and/or neuronal NO synthase (iNOS and nNOS respectively) and peroxynitrite accumulation, as secondary but accelerating factors compromising the blood brain barrier (BBB). If this turns out to be the case, pharmacological interventions that target chronic hypoperfusion might ameliorate the key features of dementing neurodegeneration.	es-ES
dc.format	application/pdf
dc.language	spa
dc.publisher	Universidad Colegio Mayor de Cundinamarca	es-ES
dc.relation	https://hemeroteca.unad.edu.co/index.php/nova/article/view/408/1147
dc.rights	Derechos de autor 2008 NOVA Publicación en Ciencias Biomédicas	es-ES
dc.source	NOVA Biomedical Sciences Journal; Vol. 6 No. 10 (2008); 170-189	en-US
dc.source	Nova; Vol. 6 Núm. 10 (2008); 170-189	es-ES
dc.source	NOVA Ciências Biomédicas Publicação; v. 6 n. 10 (2008); 170-189	pt-BR
dc.source	2462-9448
dc.source	1794-2470
dc.subject	brain hypoperfusion	en-US
dc.subject	mitochondria	en-US
dc.subject	neurodegeneration	en-US
dc.subject	nitric oxide	en-US
dc.subject	oxidation	en-US
dc.subject	oxidative stress	en-US
dc.subject	vasoactive substances.	en-US
dc.subject	brain hypoperfusion	es-ES
dc.subject	mitochondria	es-ES
dc.subject	neurodegeneration	es-ES
dc.subject	nitric oxide	es-ES
dc.subject	oxidation	es-ES
dc.subject	oxidative stress	es-ES
dc.subject	vasoactive substances.	es-ES
dc.title	Falla mitocondrial oxidativa inducida por estrés y sustancias vasoactivas como los iniciadores dominantes de la patología favorecen la reclasificación de la enfermedad de Alzheimer como una Vasocognopatía	en-US
dc.title	Oxidative stress-induced mitochondrial failure and vasoactive substances as key initiators of pathology favor the reclassification of Alzheimer Disease as a vasocognopathy	es-ES
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/publishedVersion
dc.type	reviewArticle	en-US
dc.type	reviewArticle	es-ES
dc.type	reviewArticle	pt-BR