TY - JOUR
T1 - Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes
AU - Farfán-García Eunice, Dalet
AU - Trujillo-Ferrara José, Guadalupe
AU - Castillo-Hernández María del, Carmen
AU - Guerra-Araiza Christian, Humberto
AU - Soriano-Ursúa Marvin, Antonio
PY - 2013
Y1 - 2013
N2 - 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 selec-tivity 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 or-thosteric 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 dopa-mine 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.
AB - 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 selec-tivity 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 or-thosteric 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 dopa-mine 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.
KW - Alzheimer's disease
KW - Biased signaling
KW - Drug design
KW - G-protein coupled receptors
KW - Grants-supported paper
KW - Mine receptors
KW - Muscarinic receptors
KW - Neural regeneration
KW - Neuroregeneration
KW - Oligomerization
KW - Parkinson's disease
KW - Structural biology
KW - Tive disorders
UR - http://www.scopus.com/inward/record.url?scp=84886701796&partnerID=8YFLogxK
U2 - 10.3969/j.issn.1673-5374.2013.24.009
DO - 10.3969/j.issn.1673-5374.2013.24.009
M3 - Artículo
SN - 1673-5374
VL - 8
SP - 2290
EP - 2302
JO - Neural Regeneration Research
JF - Neural Regeneration Research
IS - 24
ER -