SUMMARY OF RESEARCH

The research goal of the Gonzalez-Rey laboratory consists of knowing the relationship between the central nervous system (CNS) and the immune system, characterizing the connection between infectious diseases and their effects in neurodegenerative disorders, and in processes of pathological aging. Our investigation focuses particularly on identifying endogenous mediators shared by both systems (neuropeptides) able to tune the immune system and to restore homeostasis under inflammation, autoimmunity and infection, with a therapeutic profile on these disorders and / or that have relevancy in the development and evolution of the above mentioned diseases. Specifically, we are interested in characterizing the therapeutic effect of these neuropeptides in neuroinflammatory/neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease; in the study of their mechanisms of action; in the characterization of the neuroprotective and/or neuroregenerative effects of these molecules during the whole life of the individual, including the oldness. On the other hand, we have recently described that some of these neuropeptides have additional functions showing similar structural characteristics and functional behaviour that those exerted by antimicrobial peptides. In this respect, we are studying the possible relationship that could exist between these antimicrobial neuropeptides and the potential protective effect in the development of aging-associated disorders.

Research Aims:

1.-To identify and characterize endogenous mechanisms (neuropeptides produced by the immune and neuro-endocrine systems) able to restore homeostasis under inflammation, autoimmunity and infection. We are interested in:
- characterizing the therapeutic effect of these neuropeptides in neuroinflammatory/neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease; - studying their mechanisms of action in resident cells of the SNC and of peripheral immune tissues;
- characterizing the potential neuroprotective/neuroregenerative activity of these molecules and the dependence/independence of their immunomodulatory action.
- analyzing the consequences of the changes in the basal amounts of these neuropeptides during aging and the relationship between these variations with aging-associated degenerative diseases, as the mentioned ones.

2.-On the other hand, recently we have discovered that some of these anti-inflammatory neuropeptides have an antimicrobial role. In this respect, we are studying:
- the therapeutic activity and the mechanisms involved in the antimicrobial effect of these peptides.
- the consequences derived from the endogenous absence of these peptides in relation to suffering a major / minor susceptibility to infections.
- the presence of these peptides in barriers of defense in different organisms, to characterize their evolution from organisms in which there is not an organized nervous system.
- the relation between the susceptibility to suffer infections when there are changes in the levels, presence / absence of these antimicrobial neuropeptides
- the possible development of neurodegenerative / neurodegenerative diseases and psiquiatric disorders in the absent of these antimicrobial neuropeptides due to immune alterations derived from uncontrolled processes of infection / inflammation suffered during the whole life.

FUNDING AGENCIES LAST 5 YEARS

- Cortistatina y Envejecimiento saludable: ¿posible
piedra Rosettaa en la comunicación de los sistemas inmunitario y nervioso?. PROYECTO, J.A.- Retos de la sociedad andaluza 2021, Ref: P21_00867, (2022 - 2025).

- CORTISTATINA: COMO SUPERAR EL OBSTACULO TRASLACIONAL DEL ACCIDENTE CEREBROVASCULAR ISQUEMICO. PROYECTO, PN2020 - Proyectos I+D+i «Retos Investigación», Ref: PID2020-119638RB-I00, (2021 - 2025).

- Efecto de la cortistatina sobre la permeabilidad de la barrera hematoencefálica: Papel de las modificaciones postransduccionales de VE-cadherina. PROYECTO, , Ref: 20190E027, (2019 - 2019).

- CARACTERIZACION DEL PAPEL DE CORTISTATINA EN LA DESREGULACION INMUNOLOGICA SUBYACENTE EN LA ISQUEMIA CEREBRAL. PROYECTO, PN2017 - PROY I+D+I - PRG. RETOS DE LA SOCIEDAD, Ref: SAF2017-85602-R, (2018 - 2021).

PUBLICATIONS LAST 5 YEARS

-Paola Alejandra Romecín; Meritxell Vinyoles; Belén López-Millán; Rafael Diaz de la Guardia; Noemi M Atucha; Sergi Querol; Clara Bueno; Raquel Benitez; Elena Gonzalez-Rey; Mario Delgado; Pablo Menéndez, Robust In Vitro and In Vivo Immunosuppressive and Anti-inflammatory Properties of Inducible Caspase-9-mediated Apoptotic Mesenchymal Stromal/Stem Cell, Stem Cells Translational Medicine, 2022, Vol. 11: 88-96, ARTÍCULO, Id:892524

-Ana Isabel Sánchez-Castillo; M. Rosario Sepúlveda; José Luis Marín-Teva; Miguel A. Cuadros; David Martín-Oliva; Elena González-Rey; Mario Delgado; Veronika E. Neubrand, Switching Roles: Beneficial Effects of Adipose Tissue-Derived Mesenchymal Stem Cells on Microglia and Their Implication in Neurodegenerative Diseases, Biomolecules, 2022, Vol. 12: 2192-219, ARTÍCULO DE REVISIÓN, Id:870212

-Belmonte-Reche, E.; Peñalver, P.; Caro-Moreno, M.; Mateos-Martín, M.L.; Adán, N.; Delgado, M.; González-Rey, E.; Morales, J.C., Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases, European Journal of Medicinal Chemistry, 2021, Vol. 223: 113655, ARTÍCULO, Id:852375

-Falo, C.P.; Benitez, R.; Caro, M.; Morell, M.; Forte-Lago, I.; Hernandez-Cortes, P.; Sanchez-Gonzalez, C.; O¿valle, F.; Delgado, M.; Gonzalez-Rey, E., The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury, Pharmaceutics, 2021, Vol. 13: 7-947, ARTÍCULO, Id:852220

-Rol, Á.; Todorovski, T.; Martin-Malpartida, P.; Escolà, A.; Gonzalez-Rey, E.; Aragón, E.; Verdaguer, X.; Vallès-Miret, M.; Farrera-Sinfreu, J.; Puig, E.; Fernández-Carneado, J.; Ponsati, B.; Delgado, M.; Riera, A.; Macias, M.J., Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease, Nature Communications, 2021, Vol. 12: 1-1869, ARTÍCULO, Id:846339

-de la Guardia, R.D.; Lopez-Millan, B.; Roca-Ho, H.; Bueno, C.; Gutiérrez-Agüera, F.; Fuster, J.L.; Anguita, E.; Zanetti, S.R.; Vives, S.; Nomdedeu, J.; Sackstein, R.; Lavoie, J.; Gónzalez-Rey, E.; Delgado, M.; Rosu-Myles, M.; Menendez, P., Bone marrow mesenchymal stem/stromal cells from risk-stratified acute myeloid leukemia patients are anti-inflammatory in in vivo preclinical models of hematopoietic reconstitution and severe colitis, Haematologica, 2019, Vol. 104: e54-e58, CARTA AL EDITOR, Id:744444

-Benitez, R.; Delgado-Maroto, V.; Caro, M.; Forte-Lago, I.; Duran-Prado, M.; O¿Valle, F.; Lichtman, A.H.; Gonzalez-Rey, E.; Delgado, M., Vasoactive intestinal peptide ameliorates acute myocarditis and atherosclerosis by regulating inflammatory and autoimmune responses, Journal of Immunology, 2018, Vol. 200: 3697-3710, ARTÍCULO, Id:723202

-Martínez-García, M.; Bart, J.M.; Campos-Salinas, J.; Valdivia, E.; Martínez-Bueno, M.; González-Rey, E.; Navarro, M.; Maqueda, M.; Cebrián, R.; Pérez-Victoria, J.M., Autophagic-related cell death of Trypanosoma brucei induced by bacteriocin AS-48, International Journal for Parasitology: Drugs and Drug Resistance, 2018, Vol. 8: 203-212, ARTÍCULO, Id:716667

-Pablo Peñalver; Efres Belmonte-Reche; Norma Adán; Marta Caro; María Luisa Mateos-Martín; Mario Delgado; Elena González-Rey; Juan Carlos Morales, Alkylated resveratrol prodrugs and metabolites as potential therapeutics for neurodegenerative diseases, European Journal of Medicinal Chemistry, 2018, Vol. 146: 123-138, ARTÍCULO, Id:713336

DOCTORAL THESES LAST 5 YEARS