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
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morales et al., ludis. (2008). 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. NOVA, 6(10). https://doi.org/10.22490/24629448.408
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ludis morales et al.
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La enfermedad de Alzheimer y el accidente cerebrovascular son dos causas que conducen a la demencia relativa a la edad. El aumento de la evidencia apoya la idea de que la hipoperfusión crónica es sobre todo responsable de la patogénesis que es la base de ambos procesos de la enfermedad. La hipoperfusión se asocia al desequilibrio oxidativo, en gran parte debido a las especies reactivas del oxígeno, que se asocian a otros desórdenes degenerativos relativos a la edad. Evidencia reciente indica que un estímulo crónico de lesión induce la hipoperfusión vista en la microcirculación de las regiones vulnerables del cerebro. Esto conduce a la falta de energía, manifestada por daño a la ultraestructura mitocondrial. Los trastornos mitocondriales conducen a la formación de una gran cantidad de mitocondrias “hipoxicas” electrón-densas y causan la sobreproducción de deleciones en el ADN mitocondrial (mtADN), debidas muy probablemente a la ruptura de la doble hélice. Además, estas anormalidades mitocondriales coexisten con la actividad redox incrementada, peroxidación lipídica y la oxidación del ARN, que son características bien establecidas de la patología de Alzheimer, antes de la aparición de los depósitos del b-amiloide.
En la enfermedad de Alzheimer, el estrés oxidativo ocurre dentro de los varios compartimientos celulares y dentro de ciertos tipos de células más que en otros, a saber el endotelio vascular, que se asocia a daño aterosclerótico, así como en las neuronas piramidales y glia. Es interesante que estas células vulnerables demuestran deleciones del mtADN y marcadores de estrés oxidativo solamente en las regiones que están cercanamente relacionadas a los vasos dañados. Esta evidencia sugiere fuertemente que la hipoperfusión crónica induce la acumulación de los productos del estrés oxidativo. Además, las lesiones de la pared vascular del cerebro se correlacionan linealmente con el grado de daño celular neuronal y glial. Por lo tanto, concluimos que la hipoperfusión crónica es un iniciador clave del estrés oxidativo en varias células parénquimales del cerebro, y las mitocondrias parecen ser blancos primarios para el daño de cerebro en la enfermedad de Alzheimer. En este trabajo, delineamos el papel de la acumulación continua de los productos del estrés oxidativo, tales como una abundancia de productos de óxido nítrico (vía la sobreexpresión de NO sintasa inducible y/o neuronal (iNOS y nNOS respectivamente) y de acumulación del peroxinitrito, como factores secundarios pero acelerantes que comprometen la barrera hematoencefálica. Si éste resulta ser el caso, las intervenciones farmacológicas que apuntan a la hipoperfusion crónica pudieran mejorar las características dominantes de la demencia neurodegenerativa.
En la enfermedad de Alzheimer, el estrés oxidativo ocurre dentro de los varios compartimientos celulares y dentro de ciertos tipos de células más que en otros, a saber el endotelio vascular, que se asocia a daño aterosclerótico, así como en las neuronas piramidales y glia. Es interesante que estas células vulnerables demuestran deleciones del mtADN y marcadores de estrés oxidativo solamente en las regiones que están cercanamente relacionadas a los vasos dañados. Esta evidencia sugiere fuertemente que la hipoperfusión crónica induce la acumulación de los productos del estrés oxidativo. Además, las lesiones de la pared vascular del cerebro se correlacionan linealmente con el grado de daño celular neuronal y glial. Por lo tanto, concluimos que la hipoperfusión crónica es un iniciador clave del estrés oxidativo en varias células parénquimales del cerebro, y las mitocondrias parecen ser blancos primarios para el daño de cerebro en la enfermedad de Alzheimer. En este trabajo, delineamos el papel de la acumulación continua de los productos del estrés oxidativo, tales como una abundancia de productos de óxido nítrico (vía la sobreexpresión de NO sintasa inducible y/o neuronal (iNOS y nNOS respectivamente) y de acumulación del peroxinitrito, como factores secundarios pero acelerantes que comprometen la barrera hematoencefálica. Si éste resulta ser el caso, las intervenciones farmacológicas que apuntan a la hipoperfusion crónica pudieran mejorar las características dominantes de la demencia neurodegenerativa.
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123 Moreira PI, Nunomura A, Nakamura M, Takeda A, Shenk JC, Aliev G, Smith MA, Perry G. Nucleic acid oxidation in Alzheimer disease. Free Radic Biol Med. 2006;44:1493-1505.
124. Moreira PI, Siedlak SL, Wang X, Santos MS, Oliveira CR, Tabaton M, Nunomura A, et al. Increased Autophagic Degradation of Mitochondria in Alzheimer Disease. Autophagy. 2007;3:614-615.
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DOI: http://dx.doi.org/10.22490/24629448.408
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3. Aliev G, Shenk JC, Fischbach K, Perry G. Stem cell niches as clinical targets: the future of anti-ischemic therapy? Nat Clin Pract Cardiovasc Med. 2008;5:590-591.
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122. Aliyev A, Chen SG, Seyidova D, Smith MA, Perry G, de la Torre J, Aliev G. Mitochondria DNA deletions in atherosclerotic hypoperfused brain microvessels as a primary target for the development of Alzheimer’s disease. J Neurol Sci. 2005;229-230:285-292.
123 Moreira PI, Nunomura A, Nakamura M, Takeda A, Shenk JC, Aliev G, Smith MA, Perry G. Nucleic acid oxidation in Alzheimer disease. Free Radic Biol Med. 2006;44:1493-1505.
124. Moreira PI, Siedlak SL, Wang X, Santos MS, Oliveira CR, Tabaton M, Nunomura A, et al. Increased Autophagic Degradation of Mitochondria in Alzheimer Disease. Autophagy. 2007;3:614-615.
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DOI: http://dx.doi.org/10.22490/24629448.408
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