{"id":54807,"date":"2022-07-05T11:24:39","date_gmt":"2022-07-05T09:24:39","guid":{"rendered":"https:\/\/blog.uchceu.es\/farmacia\/?p=54807"},"modified":"2022-07-23T20:36:48","modified_gmt":"2022-07-23T18:36:48","slug":"la-bradicinina-y-su-relacion-con-la-enfermedad-de-alzheimer","status":"publish","type":"post","link":"https:\/\/blog.uchceu.es\/farmacia\/la-bradicinina-y-su-relacion-con-la-enfermedad-de-alzheimer\/","title":{"rendered":"La bradicinina y su relaci\u00f3n con la Enfermedad de Alzheimer"},"content":{"rendered":"\n<p>Como ya hemos visto en<a href=\"https:\/\/blog.uchceu.es\/farmacia\/deterioro-cognitivo-y-demencia-que-es-y-cuales-son-sus-tipos\/\" target=\"_blank\" rel=\"noreferrer noopener\"> blogs anteriores<\/a>, la <strong>Enfermedad de Alzheimer<\/strong> (EA) es una de las principales<strong> causas <\/strong>de deterioro cognitivo y cuya <strong>etiolog\u00eda exacta<\/strong> sigue desconocida, destacando, entre otras mol\u00e9culas, la <strong>bradicinina<\/strong>. <\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Etiolog\u00eda de la Enfermedad de Alzheimer<\/strong><\/h3>\n\n\n\n<p>Pese a que existen m\u00faltiples teor\u00edas que indican su causa, los principales elementos implicados y que se emplean en la actualidad para su diagn\u00f3stico son la formaci\u00f3n de <strong>placas amiloides<\/strong> y la <strong>fosforilaci\u00f3n<\/strong> de la prote\u00edna <strong>tau<\/strong>. <\/p>\n\n\n\n<p>En concreto, cambios o <strong>mutaciones<\/strong> en la <strong>prote\u00edna precursora amiloide<\/strong> originan la formaci\u00f3n de las <strong>placas de beta \u2013 amiloide (\u00dfA)<\/strong>, la cual se acumula a nivel cerebral. Ello produce <strong>da\u00f1o cerebral<\/strong> por tres v\u00edas diferentes: <strong>disfunci\u00f3n mitocondrial<\/strong> y <strong>excitotoxicidad<\/strong>, <strong>hiperfosforilaci\u00f3n de tau<\/strong> e <strong>inflamaci\u00f3n<\/strong>. <\/p>\n\n\n\n<p>Cuando este darse<strong> da\u00f1o <\/strong>neuronal ocurre, las<strong> c\u00e9lulas gliales<\/strong> lo detectan e intentan <strong>fagocitar <\/strong>el mayor n\u00famero de mol\u00e9culas de<strong> \u00dfA<\/strong>. no obstante, cuando este sistema se satura y deja de ser eficiente, se liberan mol\u00e9culas proinflamatorias que favorecen la <strong>acumulaci\u00f3n de \u00dfA<\/strong>, <strong>muerte celular<\/strong> y la producci\u00f3n de <strong>especies reactivas de ox\u00edgeno<\/strong>. <\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Bradicinina<\/strong><\/h3>\n\n\n\n<p>La bradicinina es una mol\u00e9cula<strong> vasodilatadora <\/strong>que se forma a partir del sistema calicre\u00edna \u2013 cinina. Del mismo modo, su formaci\u00f3n tambi\u00e9n est\u00e1 implicada la cascada de coagulaci\u00f3n, en concreto con el <strong>factor XIIa<\/strong>. Este favorece la transformaci\u00f3n de la precalicre\u00edna plasm\u00e1tica en calicre\u00edna plasm\u00e1tica, la cu\u00e1l a su vez, favorece la formaci\u00f3n de bradicinina a partir de cinin\u00f3geno de bajo peso molecular.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Bradicinina y enfermedad de alzheimer<\/strong><\/h4>\n\n\n\n<p>Seg\u00fan estudios recientes, la bradicinina podr\u00eda estar implicada en la EA. Su relaci\u00f3n podr\u00eda estar en que la bradicinina interviene en el proceso de inflamaci\u00f3n, favoreciendo la acumulaci\u00f3n de placas de \u00dfA. Dicho efecto depender\u00e1, en parte, del receptor de bradicinina que se vea afectado.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\"><strong>Receptores de bradicinina<\/strong><\/h5>\n\n\n\n<p>Existen dos receptores de bradicinina. Ambos se expresan en las c\u00e9lulas de la microgl\u00eda y astrocitos, pero sus mecanismos de acci\u00f3n son distintos:<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Recetor B1: <\/strong>Es <strong>inducible<\/strong>. Este factor disminuye la concentraci\u00f3n de Ca<sup>2+<\/sup> intracelular y produce inflamaci\u00f3n cr\u00f3nica, liberando diferentes citosinas inflamatorias como, por ejemplo, TNFa. Adem\u00e1s, favorece la hiperfosforilaci\u00f3n de tau, provoca estr\u00e9s oxidativo y da\u00f1o en la barrera hematoencef\u00e1lica.<\/li><li><strong>Receptor B2: <\/strong>Es constitutivo. Produce inflamaci\u00f3n aguda y aumenta la concentraci\u00f3n de Ca<sup>2+<\/sup> intracelular, favoreciendo la muerte celular. Adem\u00e1s, el antagonismo de este receptor disminuye la memoria espacial en ratones y aumenta el estr\u00e9s oxidativo, la hiperfosforilaci\u00f3n de tau y el da\u00f1o en la barrera hematoencef\u00e1lica. Cabe destacar que, B2 libera BDNF (factor neurotr\u00f3fico derivado del cerebro), factor que activa v\u00edas de supervivencia celular.<\/li><\/ul>\n\n\n\n<p>Por todo ello, las teor\u00edas m\u00e1s recientes se inclinan a afirmar que el receptor B1 podr\u00eda ser perjudicial y el receptor B2 podr\u00eda tener un papel neuroprotector.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>F\u00e1rmacos relacionados con el metabolismo de la bradicinina<\/strong><\/h4>\n\n\n\n<p>Finalmente, existen numerosos <strong>f\u00e1rmacos<\/strong> que intervienen en el <strong>mecanismo de acci\u00f3n <\/strong>de la <strong>bradicinina<\/strong>, ya sea, aumentando o disminuyendo su concentraci\u00f3n o actuando en alguno de sus receptores. <\/p>\n\n\n\n<div class=\"wp-block-image is-style-default\"><figure class=\"alignright size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/blog.uchceu.es\/farmacia\/wp-content\/uploads\/sites\/5\/2022\/07\/pexels-ready-made-3850735-2-650x433.jpg\" alt=\"F\u00e1rmacos relacionados con la enfermedad de alzheimer\" class=\"wp-image-54814\" width=\"357\" height=\"238\" srcset=\"https:\/\/blog.uchceu.es\/farmacia\/wp-content\/uploads\/sites\/5\/2022\/07\/pexels-ready-made-3850735-2-650x433.jpg 650w, https:\/\/blog.uchceu.es\/farmacia\/wp-content\/uploads\/sites\/5\/2022\/07\/pexels-ready-made-3850735-2-315x210.jpg 315w, https:\/\/blog.uchceu.es\/farmacia\/wp-content\/uploads\/sites\/5\/2022\/07\/pexels-ready-made-3850735-2-768x512.jpg 768w, https:\/\/blog.uchceu.es\/farmacia\/wp-content\/uploads\/sites\/5\/2022\/07\/pexels-ready-made-3850735-2-1536x1024.jpg 1536w, https:\/\/blog.uchceu.es\/farmacia\/wp-content\/uploads\/sites\/5\/2022\/07\/pexels-ready-made-3850735-2-2048x1365.jpg 2048w, https:\/\/blog.uchceu.es\/farmacia\/wp-content\/uploads\/sites\/5\/2022\/07\/pexels-ready-made-3850735-2-696x464.jpg 696w, https:\/\/blog.uchceu.es\/farmacia\/wp-content\/uploads\/sites\/5\/2022\/07\/pexels-ready-made-3850735-2-1068x712.jpg 1068w, https:\/\/blog.uchceu.es\/farmacia\/wp-content\/uploads\/sites\/5\/2022\/07\/pexels-ready-made-3850735-2-630x420.jpg 630w\" sizes=\"auto, (max-width: 357px) 100vw, 357px\" \/><\/figure><\/div>\n\n\n\n<ul class=\"wp-block-list\"><li>F\u00e1rmacos que podr\u00edan <strong>aumentar<\/strong> la concentraci\u00f3n de <strong>bradicinina<\/strong>: Ejemplo de ello son los Inhibidores de la Enzima Convertidora de Angiotensina (<em>IECAs<\/em>) y el <em>entresto (valsart\u00e1n\/sacubitril)<\/em>. El primer grupo inhibe la ECA, mientras que el segundo act\u00faa sobre la neprilisina, siendo ambas enzimas degradadoras de bradicinina. <\/li><li>F\u00e1rmacos que <strong>disminuye<\/strong>n la <strong>bradicinina<\/strong>: Ejemplo de ello son <em>berinert (inhibidor estearasa C1), lanadelumab, heparina, anbinex, atenativ, kybernin <\/em>y<em> apotrinina<\/em>, ya que, inhiben alguno de los factores implicados en su formaci\u00f3n. <\/li><li>F\u00e1rmacos que act\u00faan sobre <strong>receptores espec\u00edficos<\/strong>: Por otra parte, <em>icatibant <\/em>y<em> raloxifeno<\/em> act\u00faan sobre el receptor B2, mientras que la <em>noscapina<\/em> sobre el receptor B1. La relaci\u00f3n de estos f\u00e1rmacos con la enfermedad de Alzheimer no ha sido demostrada todav\u00eda y, por tanto, podr\u00eda ser una futura l\u00ednea de investigaci\u00f3n.<\/li><\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Conclusiones<\/strong><\/h3>\n\n\n\n<p>A pesar de que la causa de la enfermedad de Alzheimer es todav\u00eda desconocida, las \u00faltimas l\u00edneas de investigaci\u00f3n se indican que podr\u00eda existir una <strong>retroalimentaci\u00f3n positiva<\/strong> entre la <strong>bradicinina<\/strong> <strong>y<\/strong> las <strong>placas \u00dfA<\/strong>, dando lugar a la EA. <\/p>\n\n\n\n<p>Es decir, la bradicinina podr\u00eda favorecer la formaci\u00f3n de \u00dfA y estas, a su vez, favorecer la producci\u00f3n de la mol\u00e9cula vasodilatadora. Adem\u00e1s, muchos estudios afirman que el receptor B1 podr\u00eda estar relacionado con procesos patol\u00f3gicos, ejerciendo un papel neuroprotector el receptor B2. No obstante, se debe seguir investigando para obtener mayores conclusiones.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<pre class=\"wp-block-verse\">Art\u00edculo realizado a partir del resumen de Trabajo Fin de Grado <em>\"Bradicinina: Mecanismo de acci\u00f3n, relaci\u00f3n con la Enfermedad de Alzheimer y f\u00e1rmacos que modifican su concentraci\u00f3n\"<\/em> realizado por Mar\u00eda del Mar Garc\u00eda Zamora, alumna de 5\u00ba de Farmacia de la Universidad CEU-Cardenal Herrera. Revisado por Gemma Mar\u00eda Garc\u00eda Lluch, doctoranda en CEINDO y miembro de la C\u00e1tedra DeCo.<\/pre>\n\n\n\n<h4 class=\"wp-block-heading\">Bibliograf\u00eda destacada:<\/h4>\n\n\n\n<p>Breijyeh Z, Karaman R. Comprehensive review on Alzheimer\u2019s disease: Causes and treatment. Molecules [Internet]. 2020;25(24):5789. Disponible en: http:\/\/dx.doi.org\/10.3390\/molecules25245789 <\/p>\n\n\n\n<p>Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. The Lancet Commissions Dementia prevention, intervention, and care: 2020 report of the Lancet Commission The Lancet Commissions [Internet]. 2020 p. 413. Available from: 27 https:\/\/www.thelancet.com\/action\/showPdf?pii=S0140-&nbsp;<\/p>\n\n\n\n<p>Kandimalla R, Reddy PH. Therapeutics of neurotransmitters in Alzheimer\u2019s disease. J Alzheimers Dis [Internet]. 2017;57(4):1049\u201369. Disponible en: http:\/\/dx.doi.org\/10.3233\/jad-161118 <\/p>\n\n\n\n<p>Ni R, Kindler DR, Waag R, Rouault M, Ravikumar P, Nitsch R, et al. FMRI reveals mitigation of cerebrovascular dysfunction by bradykinin receptors 1 and 2 inhibitor noscapine in a mouse model of cerebral amyloidosis. Front Aging Neurosci [Internet]. 2019;11:27. Disponible en: http:\/\/dx.doi.org\/10.3389\/fnagi.2019.00027 <\/p>\n\n\n\n<p>Tang M-Y, Gorin FA, Lein PJ. Review of evidence implicating the plasminogen activator system in blood-brain barrier dysfunction associated with Alzheimer\u2019s disease. Ageing Neurodegener Dis [Internet]. 2022;2. Disponible en: http:\/\/dx.doi.org\/10.20517\/and.2022.05 <\/p>\n\n\n\n<p>Asraf K, Torika N, Danon A, Fleisher-Berkovich S. Involvement of the bradykinin B1 receptor in microglial activation: In vitro and in vivo studies. Front Endocrinol (Lausanne) [Internet]. 2017;8:82. Disponible en: http:\/\/dx.doi.org\/10.3389\/fendo.2017.00082 <\/p>\n\n\n\n<p>Nunes MA, Toricelli M, Sch\u00f6we NM, Malerba HN, Dong-Creste KE, Farah DMAT, et al. Kinin B2 receptor activation prevents the evolution of Alzheimer\u2019s disease pathological characteristics in a transgenic mouse model. Pharmaceuticals (Basel) [Internet]. 2020;13(10):288. Disponible en: http:\/\/dx.doi.org\/10.3390\/ph13100288 <\/p>\n\n\n\n<p>Toricelli M, Evangelista SR, Oliveira LR, Viel TA, Buck HS. Neuroprotective effects of kinin B2 receptor in organotypic hippocampal cultures of middle-aged mice. Front Aging Neurosci [Internet]. 2019;11:168. Disponible en: http:\/\/dx.doi.org\/10.3389\/fnagi.2019.00168&nbsp;<\/p>\n\n\n\n<p>Chen Z-L, Singh K, Horn K, Strickland S, Norris EH. Anti-HK antibody reveals critical roles of a 20-residue HK region for A\u03b2-induced plasma contact system activation Tracking no: ADV-2021-006612R2. 2022 <\/p>\n\n\n\n<p>Singh PK, Chen Z-L, Ghosh D, Strickland S, Norris EH. Increased plasma bradykinin level is associated with cognitive impairment in Alzheimer\u2019s patients. Neurobiol Dis [Internet]. 2020;139(104833):104833. Disponible en: http:\/\/dx.doi.org\/10.1016\/j.nbd.2020.104833 <\/p>\n\n\n\n<p>Nokkari A, Abou-El-Hassan H, Mechref Y, Mondello S, Kindy MS, Jaffa AA, et al. Implication of the Kallikrein-Kinin system in neurological disorders: Quest for potential biomarkers and mechanisms. Prog Neurobiol [Internet]. 2018;165\u2013167:26\u201350. Disponible en: http:\/\/dx.doi.org\/10.1016\/j.pneurobio.2018.01.003 <\/p>\n\n\n\n<p>Ji B, Wang Q, Xue Q, Li W, Li X, Wu Y. The dual role of kinin\/kinin receptors system in Alzheimer\u2019s disease. Front Mol Neurosci [Internet]. 2019;12:234. Disponible en: http:\/\/dx.doi.org\/10.3389\/fnmol.2019.00234&nbsp;<\/p>\n\n\n\n<p>Weidmann H, Heikaus L, Long AT, Naudin C, Schl\u00fcter H, Renn\u00e9 T. The plasma contact system, a protease cascade at the nexus of inflammation, coagulation and immunity. Biochim Biophys Acta Mol Cell Res [Internet]. 2017;1864(11):2118\u201327. Disponible en: http:\/\/dx.doi.org\/10.1016\/j.bbamcr.2017.07.009&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>En la entrada de hoy, comentamos como la bradicinina podr\u00eda contribuir a la presencia de placas amiloides patol\u00f3gicas, caracter\u00edsticas de la Enfermedad de Alzheimer.<\/p>\n","protected":false},"author":542,"featured_media":54814,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5],"tags":[387,261,262,282],"class_list":{"0":"post-54807","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-divulgacion-cientifica","8":"tag-bradicinina","9":"tag-catedra-deco","10":"tag-deterioro-cognitivo","11":"tag-enfermedad-de-alzheimer"},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.7 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>La bradicinina y su relaci\u00f3n con la Enfermedad de 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