EXPLORATION OF THE MECHANISMS OF HOMEOSTASIS OF MONOVALENT CATIONS AS A NEW ANTI-FUNGAL DIANA (Q3146485): Difference between revisions
Jump to navigation
Jump to search
(Created claim: summary (P836): INVASIVE FUNGIC INFECTIONS POSE A MAJOR HEALTH THREAT, ESPECIALLY IN IMMUNOCOMPROMISED INDIVIDUALS, WITH A MORTALITY RATE RANGING FROM 20 % TO 90 % FOR THE THREE MOST COMMON SPECIES OF HUMAN PATHOGEN FUNGI, CANDIDA ALBICANS, ASPERGILLUS FUMIGATUS AND CRYPTOCOCCUS NEOFORMANS. DESPITE THE EFFORTS INVESTED IN THE DEVELOPMENT OF NEW THERAPEUTIC STRATEGIES, ONLY A LIMITED NUMBER OF PHARMACOS ARE AVAILABLE AND MOST OF THEM ARE AIMED AT WHAT COULD CONC...) |
(Changed label, description and/or aliases in fr: translated_label) |
||
| label / fr | label / fr | ||
EXPLORATION DES MÉCANISMES DE L’HOMÉOSTASIE DES CATIONS MONOVALENTS COMME NOUVELLE DIANA ANTIFONGIQUE | |||
Revision as of 15:29, 2 December 2021
Project Q3146485 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | EXPLORATION OF THE MECHANISMS OF HOMEOSTASIS OF MONOVALENT CATIONS AS A NEW ANTI-FUNGAL DIANA |
Project Q3146485 in Spain |
Statements
114,950.0 Euro
0 references
229,900.0 Euro
0 references
50.0 percent
0 references
1 January 2015
0 references
30 June 2018
0 references
UNIVERSIDAD AUTONOMA DE BARCELONA
0 references
42°13'24.28"N, 1°53'31.70"E
0 references
08903
0 references
LAS INFECCIONES FUNGICAS INVASIVAS REPRESENTAN UNA GRAN AMENAZA PARA LA SALUD, ESPECIALMENTE EN INDIVIDUOS INMUNOCOMPROMETIDOS, CON UNA TASA DE MORTALIDAD QUE VA DESDE EL 20 AL 90% PARA LAS TRES ESPECIES MAS COMUNES DE HONGOS PATOGENOS HUMANOS, CANDIDA ALBICANS, ASPERGILLUS FUMIGATUS Y CRYPTOCOCCUS NEOFORMANS. A PESAR DE LOS ESFUERZOS INVERTIDOS EN EL DESARROLLO DE NUEVAS ESTRATEGIAS TERAPEUTICAS, SE DISPONE SOLO DE UN NUMERO LIMITADO DE FARMACOS Y LA MAYORIA DE ELLOS ESTAN DIRIGIDOS A LO QUE PODRIA CONSIDERARSE CONCEPTUALMENTE COMO DIANAS "DIFERENCIALES", TALES COMO LA PARED CELULAR (INEXISTENTE EN LOS SERES HUMANOS) O LA MEMBRANA CELULAR, DE DIFERENTE COMPOSICION LIPIDICA EN LEVADURAS Y HUMANOS. SIN EMBARGO, ESTE ARSENAL TERAPEUTICO ES CLARAMENTE INSUFICIENTE, DEBIDO A LA CRECIENTE INCIDENCIA DE INFECCIONES FUNGICAS, A LOS EFECTOS SECUNDARIOS INDESEABLES DE MUCHOS DE LOS FARMACOS ACTUALMENTE DISPONIBLES, Y AL RAPIDO DESARROLLO DE RESISTENCIAS. EN CONSECUENCIA, EL DESARROLLO DE NUEVOS ENFOQUES EN LA BUSQUEDA DE TERAPIAS ANTIFUNGICAS SE HA CONVERTIDO ES UNA NECESIDAD URGENTE. _x000D_ LA HOMEOSTASIS DE CATIONES MONOVALENTES ES UN FACTOR CLAVE PARA LA SUPERVIVENCIA DE CUALQUIER ORGANISMO, INCLUYENDO LOS HONGOS. ES DE REMARCAR QUE LOS SISTEMAS DE ENTRADA Y EFLUJO DE LOS CATIONES MONOVALENTE SON MUY DIFERENTES EN LEVADURAS Y EN HUMANOS, COMO TAMBIEN LO SON ALGUNOS DE SUS ELEMENTOS REGULADORES. SORPRENDENTEMENTE, LA POSIBILIDAD DE EXPLOTAR ESTAS DIFERENCIAS NUNCA HA SIDO EXPLORADA, A PESAR DE LA RECIENTE EVIDENCIA DE QUE LAS ALTERACIONES DE LA HOMEOSTASIS DE CATIONES EN HONGOS PATOGENOS SENSIBILIZAN A ESTOS ORGANISMOS A ANTIFUNGICOS EXISTENTES. TENEMOS LA INTENCION DE APROVECHAR NUESTRA AMPLIA EXPERIENCIA EN EL ESTUDIO DE LOS MECANISMOS QUE CONTROLAN EL FLUJO DE CATIONES EN LEVADURAS PARA INVESTIGAR, UTILIZANDO UNA COMBINACION DE METODOS BIOQUIMICOS Y GENETICOS, LA POSIBILIDAD DE DEFINIR LA INTERFERENCIA CON LA HOMEOSTASIS DE CATIONES COMO UN OBJETIVO NOVEDOSO PARA EL DESARROLLO DE ESTRATEGIAS ANTIFUNGICAS. _x000D_ NUESTRA PROPUESTA INCLUYE LA CARACTERIZACION EN PROFUNDIDAD DE LA REGULACION DE PPZ1, UN REGULADOR CRUCIAL DE LA CAPTACION DE K+ Y DE LA SALIDA DE NA+, Y CUYA DESREGULACION RESULTA EXTREMADAMENTE TOXICA PARA LA LEVADURA. TAMBIEN NOS PROPONEMOS ESTUDIAR LA CONEXION ENTRE OTROS REGULADORES DE LA HOMEOSTASIS DE IONES, COMO SON LA FAMILIA DE LAS PROTEINA QUINASA NPR1/HAL5 Y LA VIA RIM101, CON FARMACOS CON ACTIVIDAD ANTIFUNGICA. LOS RESULTADOS DE ESTE TRABAJO CLARIFICARAN LA IMPLICACION DE DETERMINADOS COMPONENTES DE LA HOMEOSTASIS DE IONES, TANTO EN EL MECANISMO DE ACCION DE TERAPIAS ANTIFUNGICAS YA ESTABLECIDAS, COMO EN LA DEFINICION DE POSIBLES DIANAS INEDITAS QUE GUIEN EL DESARROLLO DE NUEVOS FARMACOS DE USO INDIVIDUAL O EN COMBINACION CON TERAPIAS EXISTENTES. (Spanish)
0 references
INVASIVE FUNGIC INFECTIONS POSE A MAJOR HEALTH THREAT, ESPECIALLY IN IMMUNOCOMPROMISED INDIVIDUALS, WITH A MORTALITY RATE RANGING FROM 20 % TO 90 % FOR THE THREE MOST COMMON SPECIES OF HUMAN PATHOGEN FUNGI, CANDIDA ALBICANS, ASPERGILLUS FUMIGATUS AND CRYPTOCOCCUS NEOFORMANS. DESPITE THE EFFORTS INVESTED IN THE DEVELOPMENT OF NEW THERAPEUTIC STRATEGIES, ONLY A LIMITED NUMBER OF PHARMACOS ARE AVAILABLE AND MOST OF THEM ARE AIMED AT WHAT COULD CONCEPTUALLY BE CONSIDERED AS “DIFFERENTIAL” TARGETS, SUCH AS THE CELL WALL (NON-EXISTENT IN HUMANS) OR THE CELL MEMBRANE, OF DIFFERENT COMPOSITION LIPIDS IN YEASTS AND HUMANS. HOWEVER, THIS THERAPEUTIC ARSENAL IS CLEARLY INSUFFICIENT, DUE TO THE INCREASING INCIDENCE OF FUNGIC INFECTIONS, THE UNDESIRABLE SIDE EFFECTS OF MANY OF THE DRUGS CURRENTLY AVAILABLE, AND THE RAPID DEVELOPMENT OF RESISTANCE. ACCORDINGLY, THE DEVELOPMENT OF NEW APPROACHES IN THE SEARCH FOR ANTI-FUNGAL THERAPIES HAS BECOME AN URGENT NEED. _x000D_ monovalent CATION HOMEOSTASIS IS A KEY FACTOR FOR THE SUPERVIVENCE OF ANY ORGANISM, INCLUDING FONGOS. IT SHOULD BE NOTED THAT THE ENTRY AND EFFLUX SYSTEMS OF MONOVALENT CATIONS ARE VERY DIFFERENT IN YEASTS AND IN HUMANS, AS ARE SOME OF THEIR REGULATORY ELEMENTS. SURPRISINGLY, THE POSSIBILITY OF EXPLOITING THESE DIFFERENCES HAS NEVER BEEN EXPLORED, DESPITE RECENT EVIDENCE THAT ALTERATIONS OF CATION HOMEOSTASIS IN PATHOGEN FUNGI SENSITISE THESE ORGANISMS TO EXISTING ANTIFUNGALS. WE INTEND TO TAKE ADVANTAGE OF OUR EXTENSIVE EXPERIENCE IN THE STUDY OF MECHANISMS THAT CONTROL THE FLOW OF CATIONS IN YEASTS TO INVESTIGATE, USING A COMBINATION OF BIOCHEMICAL AND GENETIC METHODS, THE POSSIBILITY OF DEFINING INTERFERENCE WITH CATION HOMEOSTASIS AS A NOVEL GOAL FOR THE DEVELOPMENT OF ANTI-FUNGAL STRATEGIES. _x000D_ our PROPOSES INCLUDING THE CHARACTERISATION IN PROFUNDITY OF PPZ1 REGULATION, A CRUCIAL REGULATION OF K+ CAPTACTION AND NA+ Output, AND WHY ARE DEregulation EXTREMATED TOXICAL RESULTS FOR LEVADURA. WE ALSO INTEND TO STUDY THE CONNECTION AMONG OTHER REGULATORS OF ION HOMEOSTASIS, SUCH AS THE PROTEIN KINASE FAMILY NPR1/HAL5 AND VIA RIM101, WITH PHARMACOS WITH ANTIFUNGAL ACTIVITY. THE RESULTS OF THIS STUDY WILL CLARIFY THE INVOLVEMENT OF CERTAIN COMPONENTS OF ION HOMEOSTASIS, BOTH IN THE MECHANISM OF ACTION OF ESTABLISHED ANTIFUNGAL THERAPIES, AND IN THE DEFINITION OF POSSIBLE INEDITE TARGETS THAT GUIDE THE DEVELOPMENT OF NEW PHARMACOS FOR INDIVIDUAL USE OR IN COMBINATION WITH EXISTING THERAPIES. (English)
12 October 2021
0 references
Sant Julià de Cerdanyola
0 references
Identifiers
BFU2014-54591-C2-1-P
0 references