TY - JOUR
T1 - Monoamines and their derivatives on GPCRs
T2 - Potential therapy for alzheimer’s disease
AU - Farfán-García, Eunice D.
AU - Márquez-Gómez, Ricardo
AU - Barrón-González, Mónica
AU - Pérez-Capistran, Teresa
AU - Rosales-Hernández, Martha C.
AU - Pinto-Almazán, Rodolfo
AU - Soriano-Ursúa, Marvin A.
N1 - Publisher Copyright:
© 2019 Bentham Science Publishers.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Amyloid beta
KW - Drug design
KW - GPCR
KW - Monoaminergic neuropathology
KW - Monoamines
KW - Tau-protein
UR - http://www.scopus.com/inward/record.url?scp=85075467579&partnerID=8YFLogxK
U2 - 10.2174/1570159X17666190409144558
DO - 10.2174/1570159X17666190409144558
M3 - Artículo de revisión
C2 - 30963972
AN - SCOPUS:85075467579
SN - 1567-2050
VL - 16
SP - 871
EP - 894
JO - Current Alzheimer Research
JF - Current Alzheimer Research
IS - 10
ER -