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Monoamines and their Derivatives on GPCRs: Potential Therapy for Alzheimer’s Disease

[ Vol. 16 , Issue. 10 ]

Author(s):

Eunice D. Farfán-García, Ricardo Márquez-Gómez, Mónica Barrón-González, Teresa Pérez-Capistran, Martha C. Rosales-Hernández, Rodolfo Pinto-Almazán and Marvin A. Soriano-Ursúa*   Pages 871 - 894 ( 24 )

Abstract:


Albeit cholinergic depletion remains the key event in Alzheimer’s Disease (AD), recent information describes stronger links between monoamines (trace amines, catecholamines, histamine, serotonin, and melatonin) and AD than those known in the past century. Therefore, new drug design strategies focus efforts to translate the scope on these topics and to offer new drugs which can be applied as therapeutic tools in AD. In the present work, we reviewed the state-of-art regarding genetic, neuropathology and neurochemistry of AD involving monoamine systems. Then, we compiled the effects of monoamines found in the brain of mammals as well as the reported effects of their derivatives and some structure-activity relationships. Recent derivatives have triggered exciting effects and pharmacokinetic properties in both murine models and humans. In some cases, the mechanism of action is clear, essentially through the interaction on G-protein-coupled receptors as revised in this manuscript. Additional mechanisms are inhibition of enzymes for their biotransformation, regulation of free-radicals in the central nervous system and others for the effects on Tau phosphorylation or amyloid-beta accumulation. All these data make the monoamines and their derivatives attractive potential elements for AD therapy.

Keywords:

Monoamines, monoaminergic neuropathology, drug design, GPCR, tau-protein, amyloid beta.

Affiliation:

Departamento de Fisiologia y Bioquimica. Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, 11340, Mexico City, MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, OX1 3TH, Oxford, Departamento de Fisiologia y Bioquimica. Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, 11340, Mexico City, Departamento de Fisiologia y Bioquimica. Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, 11340, Mexico City, Laboratorio de Biofisica y Biocatalisis, Seccion de Estudios de Posgrado e Investigacion Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, 11340, Mexico City, Unidad de Investigacion Hospital Regional de Alta Especialidad Ixtapaluca, Carretera Federal Mexico-Puebla km 34.5, C.P. 56530. Ixtapaluca, State of Mexico, Departamento de Fisiologia y Bioquimica. Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, 11340, Mexico City



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