{"id":30314,"date":"2021-04-01T00:00:26","date_gmt":"2021-04-01T07:00:26","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=30314"},"modified":"2021-04-04T22:13:32","modified_gmt":"2021-04-05T05:13:32","slug":"how-brain-cells-repair-their-dna-reveals-hot-spots-of-aging-and-disease","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/how-brain-cells-repair-their-dna-reveals-hot-spots-of-aging-and-disease\/","title":{"rendered":"C\u00f3mo las c\u00e9lulas cerebrales reparan su ADN revela \u201cpuntos calientes\u201d de envejecimiento y enfermedad"},"content":{"rendered":"

LA JOLLA\u2014Las neuronas carecen de la capacidad de replicar su ADN, por lo que trabajan constantemente para reparar el da\u00f1o en su genoma. Ahora, un nuevo estudio de cient\u00edficos de Salk revela que estas reparaciones no son aleatorias, sino que se centran en proteger ciertos \u201cpuntos calientes\u201d gen\u00e9ticos que parecen desempe\u00f1ar un papel cr\u00edtico en la identidad y funci\u00f3n neuronal.<\/p>\n

\"\"<\/a>
En esta imagen de un n\u00facleo de neurona, unos puntos brillantes muestran \u00e1reas de reparaci\u00f3n gen\u00e9tica enfocada.
Haga clic aqu\u00ed<\/a> para una imagen de alta resoluci\u00f3n.
Cr\u00e9dito: Instituto Salk\/Centro Avanzado de Biofot\u00f3nica Waitt<\/figcaption><\/figure>\n

Los hallazgos, publicados en el n\u00famero del 2 de abril de 2021, de Ciencia<\/em><\/a>, lo que podr\u00eda ofrecer nuevas perspectivas sobre las estructuras gen\u00e9ticas involucradas en el envejecimiento y la neurodegeneraci\u00f3n, y se\u00f1alar el desarrollo de posibles nuevas terapias para enfermedades como el Alzheimer, el Parkinson y otros trastornos de demencia relacionados con la edad.<\/p>\n

\u201cEsta investigaci\u00f3n muestra por primera vez que existen secciones del genoma que las neuronas priorizan a la hora de repararse\u201d, afirma el profesor y presidente de Salk Rusty Gage<\/a>, coautor correspondiente del art\u00edculo. \u201cEstamos entusiasmados con el potencial de estos hallazgos para cambiar la forma en que vemos muchas enfermedades relacionadas con la edad del sistema nervioso y potencialmente explorar la reparaci\u00f3n del ADN como un enfoque terap\u00e9utico\u201d.\u201d<\/p>\n

A diferencia de otras c\u00e9lulas, las neuronas generalmente no se reemplazan con el tiempo, lo que las convierte en unas de las c\u00e9lulas de mayor vida en el cuerpo humano. Su longevidad hace que sea a\u00fan m\u00e1s importante que reparen las lesiones en su ADN a medida que envejecen, para mantener su funci\u00f3n durante las d\u00e9cadas de vida de un ser humano. A medida que envejecen, la capacidad de las neuronas para realizar estas reparaciones gen\u00e9ticas disminuye, lo que podr\u00eda explicar por qu\u00e9 las personas desarrollan enfermedades neurodegenerativas relacionadas con la edad como el Alzheimer y el Parkinson.<\/p>\n

Para investigar c\u00f3mo las neuronas mantienen la salud del genoma, los autores del estudio desarrollaron una nueva t\u00e9cnica que denominaron Repair-seq. El equipo produjo neuronas a partir de c\u00e9lulas madre y les administr\u00f3 nucle\u00f3sidos sint\u00e9ticos, mol\u00e9culas que sirven como bloques de construcci\u00f3n para el ADN. Estos nucle\u00f3sidos artificiales se pudieron encontrar mediante secuenciaci\u00f3n de ADN e imaginar, mostrando d\u00f3nde las neuronas los usaron para reparar el ADN da\u00f1ado por procesos celulares normales. Si bien los cient\u00edficos esperaban ver cierta priorizaci\u00f3n, les sorprendi\u00f3 la extrema concentraci\u00f3n de las neuronas en la protecci\u00f3n de ciertas secciones del genoma.<\/p>\n

\u201cLo que vimos fueron regiones de reparaci\u00f3n incre\u00edblemente n\u00edtidas y bien definidas; \u00e1reas muy espec\u00edficas que estaban sustancialmente por encima de los niveles de fondo\u201d, dice Dylan Reid, coautor principal y coautor correspondiente, ex becario postdoctoral de Salk y ahora miembro de Vertex Pharmaceutics. \u201cLas prote\u00ednas que se encuentran en estos \u2018puntos calientes\u2019 est\u00e1n implicadas en enfermedades neurodegenerativas, y los sitios tambi\u00e9n est\u00e1n relacionados con el envejecimiento\u201d.\u201d<\/p>\n

Los autores encontraron aproximadamente 65.000 puntos cr\u00edticos que cubr\u00edan alrededor del 2 por ciento del genoma neuronal. Luego utilizaron enfoques de prote\u00f3mica para detectar qu\u00e9 prote\u00ednas se encontraban en estos puntos cr\u00edticos, implicando a muchas prote\u00ednas relacionadas con el empalme. (Estas est\u00e1n involucradas en la producci\u00f3n eventual de otras prote\u00ednas). Muchos de estos sitios parec\u00edan ser bastante estables cuando las c\u00e9lulas se trataron con agentes que da\u00f1an el ADN, y se descubri\u00f3 que los puntos cr\u00edticos de reparaci\u00f3n de ADN m\u00e1s estables estaban fuertemente asociados con sitios donde se unen las etiquetas qu\u00edmicas (\u201cmetilaci\u00f3n\u201d) que son las mejores para predecir la edad neuronal.<\/p>\n

\"Rusty
De izquierda a derecha: Rusty Gage y Dylan Reid
Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.
Cr\u00e9dito: Instituto Salk, Dylan Reid<\/figcaption><\/figure>\n

Las investigaciones anteriores se han centrado en identificar las secciones del ADN que sufren da\u00f1o gen\u00e9tico, pero esta es la primera vez que los investigadores buscan d\u00f3nde se est\u00e1 reparando intensamente el genoma.<\/p>\n

\u201cCambiamos el paradigma de buscar da\u00f1o a buscar reparaci\u00f3n, y por eso pudimos encontrar estos puntos calientes\u201d, dice Reid. \u201cEsta es biolog\u00eda realmente nueva que eventualmente podr\u00eda cambiar la forma en que entendemos las neuronas en el sistema nervioso, y cuanto m\u00e1s lo entendamos, m\u00e1s podremos buscar desarrollar terapias que aborden enfermedades relacionadas con la edad\u201d.\u201d<\/p>\n

Gage, quien ostenta la C\u00e1tedra Vi y John Adler para Investigaci\u00f3n sobre Enfermedades Neurodegenerativas Relacionadas con la Edad, a\u00f1ade: \u201cComprender qu\u00e9 \u00e1reas del genoma son vulnerables al da\u00f1o es un tema muy interesante para nuestro laboratorio. Creemos que Repair-seq ser\u00e1 una herramienta poderosa para la investigaci\u00f3n, y seguimos explorando nuevos m\u00e9todos adicionales para estudiar la integridad del genoma, particularmente en relaci\u00f3n con el envejecimiento y las enfermedades\u201d.\u201d<\/p>\n

Otros autores del estudio son Patrick Reed, Ioana Nitulescu, Enoch Tsui, Jeffrey Jones, Claire McClain, Simon Schafer, Grace Chou, Tzu-Wen Wang, Nasun Hah, Sahaana Chandran y Jesse Dixon del Salk; Johannes Schlachetzki, Addison Lana y Christopher Glass de la Universidad de California, San Diego; Ake Lu y Steve Horvath de la Universidad de California, Los \u00c1ngeles.<\/p>\n

La investigaci\u00f3n fue financiada por la American Heart Association, el Paul G. Allen Frontiers Group, la JPB Foundation, la Dolby Foundation, el Helmsley Charitable Trust y los National Institutes of Health.<\/p>","protected":false},"featured_media":30358,"template":"","faculty":[76],"disease-research":[124],"class_list":["post-30314","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-rusty-gage","disease-research-neuroscience-and-neurological-disorders"],"acf":[],"yoast_head":"\nHow brain cells repair their DNA reveals \u201chot spots\u201d of aging and disease - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/how-brain-cells-repair-their-dna-reveals-hot-spots-of-aging-and-disease\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How brain cells repair their DNA reveals \u201chot spots\u201d of aging and disease - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Neurons lack the ability to replicate their DNA, so they\u2019re constantly working to repair damage to their genome. 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