EL JUEGO DE LA VIDA Y BÚSQUEDA LOCAL

En este artículo se desarrolla e implementa un autómata celular conocido como el juego de la vida. Se define su estructura básica y se programa utilizando técnicas de búsqueda local, para hallar una solución

Unveiling the Synergistic Interplay of Neuropeptides for Novel Therapeutic Approaches in Neurodegenerative and Depressive Disorders.

The intricate relationship between hippocampal neurogenesis dysregulation and neurodegenerative diseases such as Alzheimer's, as well as depression, has sparked an urgent call for innovative therapeutic strategies. Our groundbreaking study delves into the interaction of Neuropeptide Y (NPY) and galanin (GAL) agonists, two neuromodulatory systems with a substantial presence in the limbic system, and their potential neurogenic impact on both the dorsal and ventral hippocampus. Through meticulous examination of the subchronic e"ects of NPY Y1 (Y1R) and GAL2 (GALR2) agonists on hippocampal cell proliferation, survival, and neuroprotective factor expression, we reveal a fascinating cascade of cellular responses. These include increased cell proliferation (PCNA), enhanced hippocampal cell survival (BrdU), and induction of neuroprotective factors (BDNF). Our functional assessment showcases the resulting improvements in spatial memory performance in the object-in-place task and antidepressant-like e"ects in the forced swimming test. These outcomes are attributed to the synergistic interaction between Y1R and GALR2 receptors, which promote neuronal survival and neurite outgrowth in hippocampal cells. This pioneering research paves the way for the development of heterobivalent agonist pharmacophores that target Y1R-GALR2 heterocomplexes. By acting on neuronal precursor cells in the dentate gyrus of the dorsal hippocampus, these novel compounds hold immense promise as transformative therapies for cognitive and a"ective impairments in neurodegenerative and depressive diseases.Supported by the Proy_Excel_2021_0613 (Junta de Andalucía) and Proyecto Puente (B4-2021) (UMA), Spain to MN. Swedish Medical Research Council, Sweden (62X-00715-50-3), to KF, by Stiftelsen Olle Engkvist Byggmästare to KF, and by Hjärnfonden, Sweden (F02018-0286), Hjärnfonden, Sweden (F02019-0296) and EMERGIA2020 (Junta de Andalucía), to DOBE. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

On the Role of the Balance of GPCR Homo/ Heteroreceptor Complexes in the Brain

The early work on neuropeptide-monoamine receptor-receptor interactions in the Central Nervous System gave the first indications of the existence of G protein-coupled receptors (GPCRs) heteroreceptor complexes and the GPCR field began to expand from monomers into heteromers and higher order heteromers, including also GPCR-ion channel, Receptor Tyrosine Kinases (RTK)-GPCR and Receptor activity-modifying proteins-GPCR heteroreceptor complexes. The existence of heteroreceptor complexes with allosteric receptor-receptor interactions increases the diversity of receptor function including recognition, trafficking and signalling. We have proposed the molecular phenomenon of receptor-receptor interactions as a good way to understand of how brain function can increase through molecular integration of signals. An alteration in specific receptor-receptor interactions or their balance/equilibrium (with the corresponding monomers-homomers) are indeed considered to have a role in the pathogenic mechanisms that lead to various diseases, including drug addiction, depression, Parkinson's disease and schizophrenia. Therefore, targeting protomer-protomer interactions in heteroreceptor complexes or the balance with their corresponding homoreceptor complexes in discrete brain regions may become an important field for developing novel drugs, including heterobivalent drugs and optimal types of combined treatments. Increasing our understanding of molecular integration of signals via allosteric receptor-receptor interactions in the heteroreceptor complexes will have a major impact on the molecular medicine, leading to novel strategies for drug discovery and treatment of diseases

EL JUEGO DE LA VIDA Y BÚSQUEDA LOCAL

En este artículo se desarrolla e implementa un autómata celular conocido como el juego de la vida. Se define su estructura básica y se programa utilizando técnicas de búsqueda local, para hallar una solución