Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes**
Farfán-García Eunice Dalet
Trujillo-Ferrara José Guadalupe
Castillo-Hernández María del Carmen
Guerra-Araiza Christian Humberto
Soriano-Ursúa Marvin Antonio
摘要： 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 al osteric 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. Specifical y, new possibilities are explored in relation to al osteric 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 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 musca-rinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.
机标关键词：central nervous systemmuscarinic receptorsdopamine receptorssignaling pathway
资助基金：SIP-IPN, CONACYT(CB-168116)FIS/IMSS(FIS/IMSS/PROT/G11-2/1013)
论文发表日期：2013-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：13( 2290-2302 )