title: Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes.
abstract: In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selectivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and orthosteric binding sites on dopamine receptors for the treatment of Parkinson's disease, and on muscarinic receptors for Alzheimer's disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopamine receptor holds promise as a relevant therapeutic strategy for Parkinson's disease. Regarding the treatment of Alzheimer's disease, the design of dualsteric ligands for mono-oligomeric rinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.
authors.affiliation: Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Del. Benito Juárez, Mexico City 11340, Mexico.
authors.forename: Farfán-García Eunice
authors.initials: FG
authors.lastname: Dalet
authors.affiliation: Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Del. Benito Juárez, Mexico City 11340, Mexico.
authors.forename: Trujillo-Ferrara José
authors.initials: TF
authors.lastname: Guadalupe
authors.affiliation: Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Del. Benito Juárez, Mexico City 11340, Mexico.
authors.forename: Castillo-Hernández
authors.initials: CH
authors.lastname: María Del Carmen
authors.affiliation: Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Del. Benito Juárez, Mexico City 11340, Mexico.
authors.forename: Guerra-Araiza Christian
authors.initials: GA
authors.lastname: Humberto
authors.affiliation: Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Del. Benito Juárez, Mexico City 11340, Mexico.
authors.forename: Soriano-Ursúa Marvin
authors.initials: SU
authors.lastname: Antonio
keywords: Alzheimer's disease; G-Protein coupled receptors; Parkinson's disease; biased signaling; drug design; grants-supported paper; mine receptors; muscarinic receptors; neural regeneration; neuroregeneration; oligomerization; structural biology; tive disorders