{"id":84237,"date":"2021-05-07T09:39:40","date_gmt":"2021-05-07T07:39:40","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/?p=84237"},"modified":"2021-05-07T10:12:07","modified_gmt":"2021-05-07T08:12:07","slug":"nuevas-moleculas-permiten-activar-y-desactivar-circuitos-neuronales-utilizando-luz","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/es\/nuevas-moleculas-permiten-activar-y-desactivar-circuitos-neuronales-utilizando-luz\/","title":{"rendered":"Nuevas mol\u00e9culas permiten activar y desactivar circuitos neuronales utilizando luz"},"content":{"rendered":"
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Transmisi\u00f3n sin\u00e1ptica, sistema nervioso humano, renderizado 3D<\/figcaption><\/figure>\n

El sistema nervioso de los vertebrados, incluyendo los circuitos neuronales de la m\u00e9dula espinal y del tronco del\u00a0<\/span>cerebro<\/span>, se basan entre otros, en el correcto funcionamiento de los receptores de glicina (<\/span>GlyR<\/span>). Estos receptores est\u00e1n implicados en la locomoci\u00f3n, la sensaci\u00f3n de dolor, la respiraci\u00f3n y la funci\u00f3n auditiva<\/span>,<\/span>\u00a0y\u00a0<\/span>frecuentemente<\/span>\u00a0su mal funcionamiento\u00a0<\/span>se relaciona<\/span>\u00a0con el desarrollo de trastornos neurol\u00f3gicos graves. Se han descrito muy pocos medicamentos hasta el momento capaces de modular los receptores de glicina\u00a0<\/span>y<\/span>,\u00a0<\/span>desafortunadamente,<\/span>\u00a0<\/span>no son muy espec\u00edficos\u00a0<\/span>y<\/span>\u00a0<\/span>adem\u00e1s,\u00a0<\/span>causan efectos secundarios.<\/span>\u00a0<\/span><\/p>\n

Ahora, un consorcio europeo (<\/span>Modulightor<\/span>) coordinado por el profesor de investigaci\u00f3n ICREA Pau Gorostiza, l\u00edder del grupo \u00ab<\/span>Nanoprobes<\/span>\u00a0y\u00a0<\/span>Nanoswitches<\/span><\/a>\u00bb\u00a0<\/span>en el\u00a0<\/span>IBEC y miembro del Centro de Redes de Investigaci\u00f3n Biom\u00e9dica en Bio<\/span>ingenier\u00eda<\/span>, Biomateriales y Nanomedicina (CIBER-BBN), ha desarrollado, por primera vez, mol\u00e9culas org\u00e1nicas que confieren a los\u00a0<\/span>GlyRs<\/span>\u00a0sensibilidad a la luz, denominadas\u00a0<\/span>Glyght<\/span>\u00a0y Azo-NZ1. El trabajo, publicado en dos art\u00edculos en las revistas\u00a0<\/span>eNeuro<\/span><\/i><\/a>\u00a0y\u00a0<\/span>Cell Chemical\u00a0<\/span><\/i>Biology<\/span><\/i><\/a>, muestra un control efectivo y espec\u00edfico sobre la actividad de\u00a0<\/span>GlyR<\/span>\u00a0<\/span>in vitro<\/span><\/i>\u00a0e\u00a0<\/span>in vivo<\/span><\/i>. Estas mol\u00e9culas org\u00e1nicas\u00a0<\/span>fotocr<\/span>\u00f3<\/span>mi<\/span>ca<\/span>s<\/span>\u00a0pueden ser controladas por la luz de una manera no invasiva y permiten una selectividad espacial y temporal precisa, favoreciendo la acci\u00f3n espec\u00edfica de medicamentos. Los otros laboratorios del consorcio est\u00e1n dirigidos por Carme Rovira (<\/span>Universitat<\/span>\u00a0de Barcelona), Piotr\u00a0<\/span>Bregestovski<\/span>\u00a0(Universidad\u00a0<\/span>Aix-Marseille<\/span>), y\u00a0<\/span>Burkhard<\/span>\u00a0K<\/span>\u00f6<\/span>nig<\/span>\u00a0(Universidad de\u00a0<\/span>Regensburg<\/span>).<\/span>\u00a0<\/span><\/p>\n

Glyght<\/span><\/span>\u00a0y Azo-NZ1 confieren a los receptores de glicina capaci<\/span><\/span>dad<\/span><\/span>\u00a0de respuesta a la luz<\/span><\/span>\u00a0<\/span> <\/span><\/span>\u00a0<\/span><\/strong><\/p>\n

Los receptores de glicina (<\/span>GlyRs<\/span>) son receptores inhibidores ampliamente distribuidos en el sistema nervioso central de los vertebrados y ju<\/span>e<\/span>gan un papel clave en la regulaci\u00f3n (inhibici\u00f3n) de la transmisi\u00f3n de las se\u00f1ales a trav\u00e9s de las neuronas. Est\u00e1n involucrados en trastornos como la\u00a0<\/span>hiperekplexia<\/span>\u00a0(respuesta excesiva al s<\/span>obresalto<\/span>), la sensibilizaci\u00f3n al dolor\u00a0<\/span>in<\/span>f<\/span>lamat<\/span>o<\/span>rio<\/span>, el autismo, la epilepsia del l\u00f3bulo temporal, trastornos respiratorios, el alcoholismo y enfermedades relacionadas con las neuronas motoras. Hasta hoy, solo se han descrito algunos medicamentos con las\u00a0<\/span>GlyRs<\/span>\u00a0como diana, revelando las limitaciones de la farmacolog\u00eda tradicional. Uno de los principales retos en el tratamiento de estos trastornos es encontrar compuestos que act\u00fa<\/span>e<\/span>n de una manera espacial y temporal\u00a0<\/span>muy precisa<\/span>\u00a0para obtener una acci\u00f3n espec\u00edfica del medicamento y desarrollar futuras terapias con efectos secundarios reducidos.<\/span>\u00a0<\/span><\/p>\n

En los \u00faltimos a\u00f1os, el desarrollo de la\u00a0<\/span>fotofarmacolog<\/span>\u00ed<\/span>a<\/span>, un campo que combina enfoques biol\u00f3gicos con m\u00e9todos de fotoqu\u00edmica, aparece como una alternativa al dise\u00f1o de terapias m\u00e1s seguras y eficientes basadas en mol\u00e9culas\u00a0<\/span>fotocr<\/span>\u00f3micas<\/span>, que utilizan la luz para controlar los procesos biol\u00f3gicos y estudiar la din\u00e1mica de prote\u00ednas.<\/span>\u00a0<\/span><\/p>\n

\"\"<\/p>\n

Glyght<\/span><\/span>\u00a0(del ingl\u00e9s\u00a0<\/span><\/span>GlyR<\/span><\/span>\u00a0<\/span><\/span>controlled<\/span><\/span>\u00a0<\/span><\/span>by<\/span><\/span>\u00a0light<\/span><\/span>) y Azo-NZ1 (compuesto\u00a0<\/span><\/span>fotocr<\/span><\/span>\u00f3mico<\/span><\/span>\u00a0basado en\u00a0<\/span><\/span>azoben<\/span><\/span>eno<\/span><\/span>-nitrazepam<\/span><\/span>), las nuevas mol\u00e9culas desarrolladas por los investigadores del IBEC y sus colaboradores, pueden controlar la actividad de los\u00a0<\/span><\/span>GlyRs<\/span><\/span>\u00a0de una manera dependiente de la luz. Cuando se iluminan con luz ultravioleta, cambian su configuraci\u00f3n y se unen en una regi\u00f3n espec\u00edfica del\u00a0<\/span><\/span>GlyR<\/span><\/span>, inhibiendo su funci\u00f3n.\u00a0<\/span><\/span>A su\u00a0<\/span><\/span>vez,<\/span><\/span>\u00a0la uni\u00f3n se puede\u00a0<\/span><\/span>deshacer<\/span><\/span>\u00a0con luz azul.<\/span><\/span>\u00a0<\/span><\/p>\n

La<\/span><\/span>\u00a0actividad de inhibici\u00f3n de la acci\u00f3n de\u00a0<\/span><\/span>los\u00a0<\/span><\/span>GlyRs<\/span><\/span>, apoyada por modelos\u00a0<\/span><\/span>in\u00a0<\/span><\/span>silico<\/span><\/span>, se demostr\u00f3\u00a0<\/span><\/span>in vitro<\/span><\/span>\u00a0en c\u00e9lulas de ovarios de\u00a0<\/span><\/span>hamster<\/span><\/span>\u00a0y cortes cerebrales de ratones, e\u00a0<\/span><\/span>in vivo<\/span><\/span>\u00a0en pez cebra. En los experimentos\u00a0<\/span><\/span>in vivo<\/span><\/span>, los investigadores pudieron observar claramente el efecto de\u00a0<\/span><\/span>\u201cencender y apagar\u201d<\/span><\/span>\u00a0los moduladores de\u00a0<\/span><\/span>GlyR<\/span><\/span>\u00a0sobre el comportamiento de los peces. En conjunto, los resultados muestran que estas mol\u00e9culas pueden ser herramientas \u00fatiles para controlar los circuitos neuronales en diferentes partes del sistema nervioso, como la m\u00e9dula espinal,\u00a0<\/span><\/span>el\u00a0<\/span><\/span>tronco\u00a0<\/span><\/span>cerebr<\/span><\/span>al<\/span><\/span>\u00a0<\/span><\/span>y el cerebelo.<\/span><\/span>\u00a0<\/span><\/span><\/span><\/p>\n

Los ligan<\/span><\/span>do<\/span><\/span>s con respuesta a la luz permiten controlar directamente la actividad de los receptores end\u00f3genos sin necesidad de manipulaci\u00f3n gen\u00e9tica. Se pueden aplicar a los tejidos intactos, haciendo posible las fototer<\/span><\/span>a<\/span><\/span>pi<\/span><\/span>a<\/span><\/span>s basadas en f\u00e1rmacos<\/span><\/span>.\u00a0\u00a0<\/strong><\/p>\n

Galyna Maleeva, primera autora del trabajo publicado\u00a0<\/span><\/span>en<\/span><\/span>\u00a0<\/span><\/span>eNeuro<\/span><\/span>.\u00a0<\/strong><\/p>\n<\/blockquote>\n

Los receptores de glicina son clave\u00a0<\/span><\/span>para<\/span><\/span>\u00a0el sistema nervioso<\/span><\/span><\/strong><\/h2>\n

Los\u00a0<\/span>GlyRs<\/span>\u00a0son canales de iones regulados por ligand<\/span>o<\/span>s y est\u00e1n presentes\u00a0<\/span>en\u00a0<\/span>la membrana de las neuronas,\u00a0<\/span>jugando<\/span>\u00a0un papel importante en la inhibici\u00f3n de la neurotransmisi\u00f3n\u00a0<\/span>en<\/span>\u00a0la m\u00e9dula espinal y\u00a0<\/span>en\u00a0<\/span>el tronco cerebral. Los\u00a0<\/span>GlyRs<\/span>\u00a0tambi\u00e9n son fundamentales en otros procesos fisiol\u00f3gicos y regulan la excitabilidad en la retina, el hipocampo y la am\u00edgdala, y participan en el control de<\/span>l<\/span>\u00a0movimiento, la respiraci\u00f3n y el procesamiento de la informaci\u00f3n sensorial. Cuando se activa por glicina, un amino\u00e1cido y neurotransmisor,\u00a0<\/span>GlyR<\/span>\u00a0genera una corriente de cloruro\u00a0<\/span>en<\/span>\u00a0la membrana que inhibe la transmisi\u00f3n de las se\u00f1ales a trav\u00e9s de las neuronas.<\/span>\u00a0<\/span><\/p>\n

Tanto Azo-NZ1 como\u00a0<\/span>Glyght<\/span>\u00a0causan una fuerte inhibici\u00f3n de las corrientes inducidas por glicina y representan una herramienta prometedora para las aplicaciones farmacol\u00f3gicas, as\u00ed como para la regulaci\u00f3n espec\u00edfica de la plasticidad neuronal y la excitabilidad controlada por la luz en las diferentes regiones cerebrales.<\/span>\u00a0<\/span><\/p>\n

La posibilidad de controlar estos receptores con luz es una manera prometedora de entender los circuitos neuronales que controlan<\/span><\/span>,<\/span><\/span>\u00a0y de desarrollar, en animales intactos,<\/span><\/span>\u00a0fototer<\/span><\/span>a<\/span><\/span>pi<\/span><\/span>a<\/span><\/span>s basadas en f\u00e1rmacos<\/span><\/span>.\u00a0<\/strong><\/p>\n

Alexandre Gomila, primer autor trabajo publicado\u00a0<\/span><\/span>en\u00a0<\/span><\/span>Cell Chemical\u00a0<\/span><\/span>Biology<\/span><\/span>\u00a0\u00a0<\/strong><\/p>\n<\/blockquote>\n

Estas nuevas mol\u00e9culas abren el camino al desarrollo de medicamentos que pueden modular espec\u00edficamente los receptores en cada enfermedad, reduciendo los efectos secundarios y aumentando la efectividad de los tratamientos.<\/span><\/span><\/p>\n

\n
\n

Art\u00edculos de referencia: <\/span><\/b>\u00a0<\/span><\/p>\n

Galyna<\/span>\u00a0<\/span>Maleeva<\/span>, Alba Nin-Hill, Karin\u00a0<\/span>Rustler<\/span>, Elena\u00a0<\/span>Petukhova<\/span>, Daria\u00a0<\/span>Ponomareva<\/span>, Elvira\u00a0<\/span>Mukhametova<\/span>, Alexandre MJ Gomila, Daniel\u00a0<\/span>Wutz<\/span>, Mercedes Alfonso-Prieto,\u00a0<\/span>Burkhard<\/span>\u00a0<\/span>K\u00f6nig<\/span>, Pau Gorostiza and Piotr\u00a0<\/span>Bregestovski<\/span>.\u00a0<\/span>Subunit-Specific Photocontrol of Glycine Receptors by Azobenzene-Nitrazepam\u00a0<\/span>Photoswitcher<\/span><\/a>.\u00a0<\/span>eNeuro<\/span>\u00a0(202<\/span>1<\/span>) 8 (1)<\/span>\u00a01-17<\/span>.<\/span>\u00a0<\/span><\/p>\n

Alexandre M.J. Gomila, Karin Rustler, Galyna\u00a0<\/span>Maleeva<\/span>, Alba Nin-Hill, Daniel Wutz, Antoni Bautista-<\/span>Barrufet<\/span>, Xavier Rovira, Miquel Bosch, Elvira\u00a0<\/span>Mukhametova<\/span>, Marat\u00a0<\/span>Mukhamedyarov<\/span>, Frank\u00a0<\/span>Peiretti<\/span>, Mercedes Alfonso-Prieto, Carme Rovira, Burkhard K\u00f6nig, Piotr\u00a0<\/span>Bregestovski<\/span>, Pau Gorostiza<\/span>. Photocontrol of endogenous glycine receptors in vivo.<\/span><\/a>\u00a0<\/span>Cell Chemical Biology\u00a0<\/span>(2020), 27 (11), 1425-1433.\u00a0<\/span>\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Investigadores del IBEC, en colaboraci\u00f3n con un equipo internacional, describen las primeras mol\u00e9culas capaces de regular los receptores de glicina con luz: Glyght y Azo-NZ1. Son una manera prometedora de estudiar los circuitos neuronales, desarrollar fototerapias basadas en f\u00e1rmacos de forma no invasiva, y comprender los trastornos neurol\u00f3gicos relacionados con el funcionamiento incorrecto de los receptores de glicina. <\/h3>\n","protected":false},"author":4,"featured_media":84224,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[97],"tags":[1494,1493,1152],"post_formats":[],"class_list":["post-84237","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticias-de-investigacion","tag-azo-nz1-es","tag-glyght-es","tag-pau-gorostiza-es"],"yoast_head":"\nNuevas mol\u00e9culas permiten activar y desactivar circuitos neuronales utilizando luz - Institute for Bioengineering of Catalonia<\/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:\/\/ibecbarcelona.eu\/es\/nuevas-moleculas-permiten-activar-y-desactivar-circuitos-neuronales-utilizando-luz\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Nuevas mol\u00e9culas permiten activar y desactivar circuitos neuronales utilizando luz - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Investigadores del IBEC, en colaboraci\u00f3n con un equipo internacional, describen las primeras mol\u00e9culas capaces de regular los receptores de glicina con luz: Glyght y Azo-NZ1. 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