GABA _A Receptor Family: Overview on Structural Characterization

Abstract

Indice general 5 1. Introducción Por lo anteriormente relatado esta tesis cuenta con seis capítulos: Capítulo 1: Dedicado a la descripción del problema planteado y las proteínas involucradas. Capítulo 2: Explica el desarrollo de la metodología empleada a lo largo del trabajo haciendó enfasis en los tres pilares: modelado por homología, docking molecular y simulaciones de dinámica molecular. Capítulo 3: Aborda el desarrollo del modelo y su evaluación estructural. Capítulo 4: Abarca el estudio multimetodológico de la interacción del receptor con ligandos de relevancia farmacológica y científica. Capítulo 5: Ahonda en el análisis de la interacción del receptor GABA A con DBI y sus péptidos derivados. Capítulo 6: Presenta las conclusiones finales y las proyecciones a futuro. Receptor con un GABA unido al sitio 2. Receptor con un Muscimol unido al sitio 2. Receptor con un Gabazine unido al sitio 2. Receptor con un Bicuculina unido al sitio 1. Receptor con dos GABA y un Diazepam. Receptor unido a Diazepam. Receptor unido a Flurazepam. Receptor unido a Clonazepam. Receptor unido a Flunitrazepam.

Electrophysiology of ionotropic GABA receptors

“…The study of structure-function relationships of GABA A receptors has long been hindered by the substantial diversity of conformations, making it difficult to stabilize a receptor population in a single state [43], and cryo-EM structures of GABA A receptors were only recently resolved (reviewed in [44]). GABA-binding sites are located at interfaces between subunits on the surface of the extracellular part of the receptor.…”

Efficacy and Safety of Bumetanide in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Clinical Trial

“…Cortical hyperexcitability has been recognized as a key pathogenic mechanism in ALS, promoting the development of lower motor neuron degeneration [9]. Also, common pathways of neurodegeneration in ALS seem to be linked to the excitotoxicity as chronic dysregulation of the intracellular calcium homeostasis that could be affected by dysregulation of inhibitory and excitatory synaptic neurotransmission [10]. Gamma-aminobutyric acid A (GABAA) is the most widely distributed inhibitory neurotransmitter in the adult central nervous system (CNS) and its receptors are responsible for the fastinhibitory synaptic transmission in the CNS [11].…”

Ligand-induced motions in pentameric ligand-gated ion channels revealed by EPR spectroscopy

“…While X-ray crystallography and cryo-electron microscopy have provided detailed structures of multiple pLGICs in different conformations (Amundarain, Ribeiro et al 2019), their assignment to specific functional states is difficult and molecular mechanisms underlying their allosteric gating transitions remain unclear. Some structures were determined in detergent micelles rather than in lipid bilayers, raising questions about their physiological relevance (Gonzalez-Gutierrez and Grosman 2010, daCosta and Baenziger 2013).…”