No label defined (Q3213098)
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Project Q3213098 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | No label defined |
Project Q3213098 in Spain |
Statements
106,480.0 Euro
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133,100.0 Euro
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80.0 percent
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30 December 2016
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29 December 2020
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UNIVERSIDAD DE JAEN
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37°57'20.63"N, 3°29'31.42"W
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23050
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EL ICTUS ISQUEMICO, UNA DE LAS CAUSAS DE MUERTE Y DISCAPACIDAD MAS IMPORTANTES A NIVEL MUNDIAL, ES UN PROCESO COMPLEJO EN EL QUE LA EDAD ES EL PRINCIPAL FACTOR DE RIESGO. A PESAR DE SU INCIDENCIA, NO EXISTE ACTUALMENTE UN TRATAMIENTO FARMACOLOGICO EFICAZ QUE EVITE EL DAÑO NEURODEGENERATIVO ASOCIADO A ESTA PATOLOGIA. ESTA SITUACION PROBABLEMENTE SE DEBA A LOS INNUMERABLES PROCESOS QUE SUBYACEN AL ICTUS ASI COMO AL DELICADO EQUILIBRIO ENTRE LOS MISMOS. EL DAÑO NEURONAL SE ORIGINA NO SOLO COMO CONSECUENCIA DE LA PROPIA ISQUEMIA SINO MUY ESPECIALMENTE COMO RESULTADO DEL ESTRES OXIDATIVO Y DEL ESTADO INFLAMATORIO ASOCIADOS A LA POSTERIOR FASE DE REPERFUSION. POR TANTO, EL TRATAMIENTO DEL ICTUS ISQUEMICO DEBERIA INCIDIR NO SOLO EN EL RESTABLECIMIENTO DE LA CIRCULACION NORMAL SINO TAMBIEN EN LOS MECANISMOS QUE PROMUEVEN EL DAÑO Y LA MUERTE NEURONAL. LA NEUROGLOBINA (NGB) ES UNA PROTEINA ENDOGENA CUYA CAPACIDAD NEUROPROTECTORA FRENTE AL DAÑO ISQUEMICO HA SIDO DEMOSTRADA RECIENTEMENTE. AUNQUE SU MECANISMO DE ACCION NO SE CONOCE EN PROFUNDIDAD, LA BIBLIOGRAFIA MAS RECIENTE LA RELACIONA CON SU CAPACIDAD PARA DISMINUIR EL NIVEL DE ESPECIES REACTIVAS DE OXIGENO Y NITROGENO. LA EXPRESION Y CAPACIDAD DE INDUCCION EN RESPUESTA A LA HIPOXIA DE LA NGB DISMINUYE CON LA EDAD, POR LO QUE ES MUY PROBABLE QUE LA MAYOR INCIDENCIA DE ICTUS A EDADES AVANZADAS SEA EL RESULTADO DE LA MENOR EFECTIVIDAD DE MECANISMOS NEUROPROTECTORES, EN LOS QUE LA NGB PARECE DESEMPEÑAR UN PAPEL IMPORTANTE. AUNQUE SEGUN ALGUNOS AUTORES LOS NIVELES BASALES DE ESTA PROTEINA NO GARANTIZAN LA PROTECCION FRENTE A LA MUERTE NEURONAL TRAS LA ISQUEMIA, SU SOBREEXPRESION SI CONSIGUE ESTE EFECTO. POR TANTO, LA ADMINISTRACION FARMACOLOGICA DE NGB PODRIA CONSTITUIR UNA TERAPIA EFICAZ EN EL TRATAMIENTO DEL ICTUS. DESAFORTUNADAMENTE, EL TRATAMIENTO DIRECTO CON ESTA PROTEINA NO ES POSIBLE YA QUE NO ES CAPAZ DE ATRAVESAR LA BARRERA HEMATOENCEFALICA, LO QUE HACE NECESARIO PENSAR EN ESTRATEGIAS ALTERNATIVAS, COMO POR EJEMPLO SU ASOCIACION A NANOPARTICULAS, QUE LE PERMITAN AUMENTAR SU BIODISPONIBILIDAD EN LA ZONA DEL INFARTO CEREBRAL. EN BASE A ESTOS ANTECEDENTES, ESTE PROYECTO PROPONE EL DESARROLLO DE UNA NUEVA TERAPIA FARMACOLOGICA FRENTE AL ICTUS ISQUEMICO, BASADA EN LA ACCION NEUROPROTECTORA DE LA NGB Y QUE CONSIDERE LA IMPORTANCIA DE LA EDAD. CONCRETAMENTE: 1) SE UTILIZARA UNA APROXIMACION FARMACOLOGICA, BASADA EN LA ADMINISTRACION DE NGB EXOGENA ASOCIADA A NANOVEHICULOS (LIPOSOMAS Y NANOPARTICULAS SOLIDAS LIPIDICAS), COMO HERRAMIENTA TERAPEUTICA EFICAZ QUE PERMITA AUMENTAR LA BIODISPONIBLIDAD DE LA NGB EN LA ZONA INFARTADA, GARANTIZANDO SU EFECTO NEUROPROTECTOR; 2) SE VALORARA LA EFECTIVIDAD NEUROPROTECTORA DE LOS SISTEMAS FARMACOLOGICOS SELECCIONADOS DURANTE EL ENVEJECIMIENTO, ANALIZANDO EL MECANISMO MOLECULAR IMPLICADO EN EL MISMO. ESPERAMOS QUE NUESTRA PROPUESTA CONSIGA UN IMPORTANTE AVANCE PARA UN MEJOR PRONOSTICO Y TRATAMIENTO DEL ICTUS. (Spanish)
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ISCHEMIC STROKE, ONE OF THE MOST IMPORTANT CAUSES OF DEATH AND DISABILITY WORLDWIDE, IS A COMPLEX PROCESS IN WHICH AGE IS THE MAIN RISK FACTOR. DESPITE ITS INCIDENCE, THERE IS CURRENTLY NO EFFECTIVE PHARMACOLOGICAL TREATMENT TO PREVENT NEURODEGENERATIVE DAMAGE ASSOCIATED WITH THIS PATHOLOGY. THIS SITUATION IS PROBABLY DUE TO THE INNUMERABLE PROCESSES THAT UNDERLIE THE STROKE AS WELL AS THE DELICATE BALANCE BETWEEN THEM. NEURONAL DAMAGE ORIGINATES NOT ONLY AS A RESULT OF ISCHEMIA ITSELF BUT ESPECIALLY AS A RESULT OF OXIDATIVE STRESS AND INFLAMMATORY STATE ASSOCIATED WITH THE SUBSEQUENT PHASE OF REPERFUSION. THEREFORE, THE TREATMENT OF ISCHEMIC STROKE SHOULD HAVE AN IMPACT NOT ONLY ON THE RESTORATION OF NORMAL CIRCULATION BUT ALSO ON THE MECHANISMS THAT PROMOTE NEURONAL DAMAGE AND DEATH. NEUROGLOBIN (NGB) IS AN ENDOGENOUS PROTEIN WHOSE NEUROPROTECTIVE CAPACITY AGAINST ISCHEMIC DAMAGE HAS RECENTLY BEEN DEMONSTRATED. ALTHOUGH ITS MECHANISM OF ACTION IS NOT KNOWN IN DEPTH, THE MOST RECENT BIBLIOGRAPHY RELATES IT TO ITS ABILITY TO DECREASE THE LEVEL OF REACTIVE OXYGEN AND NITROGEN SPECIES. EXPRESSION AND INDUCTION CAPACITY IN RESPONSE TO NGB HYPOXIA DECREASES WITH AGE, SO IT IS HIGHLY LIKELY THAT THE HIGHER INCIDENCE OF STROKE AT ADVANCED AGES IS THE RESULT OF THE LOWER EFFECTIVENESS OF NEUROPROTECTIVE MECHANISMS, IN WHICH NGB APPEARS TO PLAY AN IMPORTANT ROLE. ALTHOUGH ACCORDING TO SOME AUTHORS THE BASAL LEVELS OF THIS PROTEIN DO NOT GUARANTEE PROTECTION AGAINST NEURONAL DEATH AFTER ISCHEMIA, ITS OVEREXPRESSION IF IT ACHIEVES THIS EFFECT. THEREFORE, THE PHARMACOLOGICAL ADMINISTRATION OF NGB COULD BE AN EFFECTIVE THERAPY IN THE TREATMENT OF STROKE. UNFORTUNATELY, DIRECT TREATMENT WITH THIS PROTEIN IS NOT POSSIBLE SINCE IT IS NOT ABLE TO CROSS THE BLOOD-BRAIN BARRIER, WHICH MAKES IT NECESSARY TO THINK ABOUT ALTERNATIVE STRATEGIES, SUCH AS ITS ASSOCIATION TO NANOPARTICULAES, THAT ALLOW IT TO INCREASE ITS BIOAVAILABILITY IN THE BRAIN INFARCTION AREA. BASED ON THIS BACKGROUND, THIS PROJECT PROPOSES THE DEVELOPMENT OF A NEW PHARMACOLOGICAL THERAPY AGAINST ISCHEMIC STROKE, BASED ON THE NEUROPROTECTIVE ACTION OF THE NGB AND THAT CONSIDERS THE IMPORTANCE OF AGE. IN PARTICULAR: 1) A PHARMACOLOGICAL APPROACH, BASED ON THE ADMINISTRATION OF NGB EXOGENA ASSOCIATED WITH NANOVEHICULOS (LIPOSOMES AND LIPID SOLID NANOPARTICULATES), SHALL BE USED AS AN EFFECTIVE THERAPEUTIC TOOL TO INCREASE THE BIOAVAILABILITY OF NGB IN THE INFARCT ZONE, ENSURING ITS NEUROPROTECTIVE EFFECT; 2) THE NEUROPROTECTIVE EFFECTIVENESS OF THE PHARMACOLOGICAL SYSTEMS SELECTED DURING AGING WILL BE EVALUATED, ANALYSING THE MOLECULAR MECHANISM INVOLVED IN IT. WE HOPE THAT OUR PROPOSAL WILL MAKE AN IMPORTANT STEP FORWARD FOR BETTER FORECASTING AND TREATMENT OF STROKE. (English)
14 October 2021
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Jaén
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Identifiers
BFU2016-80316-R
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