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Complex diseases demand novel treatment strategies: understanding drug combination

Drug Combination Therapy 2022年第2期4卷 5-16页

作者： Renata Siqueira de Mello Vanessa Fernandes Arnaud-Sampaio Lucas Ferreira Maciel Vanessa de Sá talita glaser Henning Ulrich Claudiana Lameu Departamento de Bioquímica Instituto de QuímicaUniversidade de São PauloSPBrazil

For many multigene or multifactorial diseases,the one-drug therapy for inhibiting a defined molecular target is often less effective than combined ***,drug combination therapies are multitargeted,so the mechanisms or even interactions are often *** drug-drug interactions may promote alteration of pharmacokinetic or pharmacodynamic activities of one drug by another *** interactions may change the expected effect of medications through polymorphisms that alter the expression or activity of the drug-mediated enzyme and the cell signaling cascade,such as drug-gene interactions and drug-drug-gene *** number of possible existing interactions requires appropriate methods of *** this review,we summarized combination therapies for cancer,as well as for viral,cardiovascular,and neurological ***,we also highlight known methodologies,such as in vitro methods based on Loewe’s and Bliss’s pioneer models and in silico methods based on online available *** more elaborate methods and reliable results,multitarget therapies through drug combinations may increasingly benefit patients suffering from complex diseases.

关键词： drug combinations multitarget therapy combination therapy drug-drug interaction in vitro in silico methods and models

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Purinergic Receptors in Basal Ganglia Diseases:Shared Molecular Mechanisms between Huntington’s and Parkinson’s Disease

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Neuroscience Bulletin 2020年第11期36卷 1299-1314页

作者： talita glaser Roberta Andrejew Agatha Oliveira-Giacomelli Deidiane Elisa Ribeiro Lucas Bonfim Marques Qing Ye Wen-Jing Ren Alexey Semyanov Peter Illes Yong Tang Henning Ulrich Department of Biochemistry Institute of ChemistryUniversity of Sao PauloAv.Prof.Lineu Prestes 74&Sao PauloSP 05508-000Brazil Key Laboratory of Sichuan Province for Acupuncture and Chronobiology Chengdu 610075China Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of SciencesMoscow 117997Russia Sechenov First Moscow State Medical University Moscow 119992Russia Rudolf-Boehm-Institut ftir Pharmakologie und Toxikologie Universitat LeipzigLeipzig 04107Germany International Collaborative Centre on Big Science Plan for Purine Signaling Chengdu University of Traditional Chinese MedicineChengdu 610075China

Huntington’s(HD)and Parkinson’s diseases(PD)are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms,*** review here the participation of purinergic receptors through intracellular Ca^2+signaling in these neurodegenerative *** adenosine A2A receptor stimulates striatopallidal GABAergic neurons,resulting in inhibitory actions on GABAergic neurons of the globus pallidus.A2A and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition,and A2A receptor activation results in motor ***,the A2A receptor physically and functionally interacts with glutamate receptors,mainly with the mGlu5 receptor *** interaction facilitates glutamate release,resulting in NMDA glutamate receptor activation and an increase of Ca2+influx.P2X7 receptor activation also promotes glutamate release and neuronal ***,modulation of purinergic receptor activity,such as A2A and P2X7 receptors,and subsequent aberrant Ca^2+signaling,might present interesting therapeutic potential for HD and PD.

关键词： Purinergic receptor Central nervous system Huntington’s disease Parkinson’s disease 6-hydroxydopamine

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