Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy ...Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.展开更多
Parkinson’s disease (P D) is a com plex neu rodegenerative disorder for which ra re and common genetic variants contribute to disease risk,onset,and progression.The genetic contribution to PD can be classified mainly...Parkinson’s disease (P D) is a com plex neu rodegenerative disorder for which ra re and common genetic variants contribute to disease risk,onset,and progression.The genetic contribution to PD can be classified mainly in,first,rare DNA variants that are highly penetrant and therefore causal,which are typically associated with monogenic PD;and second,more common risk polymorphic variants,which individually exert a small increase in the risk of the disease,which are usually identified in the most prevalent and apparently sporadic PD (Blauwendraat et al.,2020).展开更多
The basal ganglia （BG） assemble a series of deep gray matter structures forming recurrent loops that include the cortex and thalamus, and that participate in the regulation of a plethora of brain functions, includin...The basal ganglia （BG） assemble a series of deep gray matter structures forming recurrent loops that include the cortex and thalamus, and that participate in the regulation of a plethora of brain functions, including elicitation and learning of reward-and aversive stimuli-associated behaviors, motor activity control and sensorimotor gating （Brom- berg-Martin et al., 2010）.展开更多
Dear Editor,The severe coagulation syndrome in numerous organs is the major life-threatening conditions characterizing the acute infection by SARS-CoV-2.Endothelial inflammation/dysfunction,platelet hyper-reactivity,g...Dear Editor,The severe coagulation syndrome in numerous organs is the major life-threatening conditions characterizing the acute infection by SARS-CoV-2.Endothelial inflammation/dysfunction,platelet hyper-reactivity,generation of neutrophil extracellular traps,promote the activation of the coagulation cascade in an infection-dependent manner.^(1)展开更多
Three recent articles published in Cell1,2 and Cell Research3 have reported multiple cryo-electron microscopy(cryo-EM)structures of the D1 dopamine receptor(DRD1)bound to either dopamine,various DRD1 agonists,or a pos...Three recent articles published in Cell1,2 and Cell Research3 have reported multiple cryo-electron microscopy(cryo-EM)structures of the D1 dopamine receptor(DRD1)bound to either dopamine,various DRD1 agonists,or a positive allosteric modulator(PAM),while in complex with the active heterotrimeric Gs protein.These studies describe for the first time active-state structures of the DRD1,an exciting advancement in the field that will allow for a better understanding of selective agonist binding,DRD1 activation,G protein selectivity,and the provision of multiple templates to facilitate future drug design and discovery for this important therapeutic target.展开更多
文摘Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.
基金supported by the intra mural funds of the National Institute in drug abuse (ZIA DA000493)(to SF)projects PID2019-109240RB-I00(to LP) and PID2020-118511RB-I00 (to FC) were founded by MCIN/AEI/10.13039/501100011033,"ERDF A way of making Europe"。
文摘Parkinson’s disease (P D) is a com plex neu rodegenerative disorder for which ra re and common genetic variants contribute to disease risk,onset,and progression.The genetic contribution to PD can be classified mainly in,first,rare DNA variants that are highly penetrant and therefore causal,which are typically associated with monogenic PD;and second,more common risk polymorphic variants,which individually exert a small increase in the risk of the disease,which are usually identified in the most prevalent and apparently sporadic PD (Blauwendraat et al.,2020).
基金supported by MINECO/ISCⅢ(SAF2014-55700-P and PIE14/00034)IWT(SBO-140028)+2 种基金Fundacióla Maratóde TV3(Grant 20152031)to FCFC and VFD belong to the“Neuropharmacology and Pain”accredited research group(Generalitat de Catalunya,2014 SGR 1251)the intramural funds of the National Institute on Drug Abuse to SF
文摘The basal ganglia （BG） assemble a series of deep gray matter structures forming recurrent loops that include the cortex and thalamus, and that participate in the regulation of a plethora of brain functions, including elicitation and learning of reward-and aversive stimuli-associated behaviors, motor activity control and sensorimotor gating （Brom- berg-Martin et al., 2010）.
文摘Dear Editor,The severe coagulation syndrome in numerous organs is the major life-threatening conditions characterizing the acute infection by SARS-CoV-2.Endothelial inflammation/dysfunction,platelet hyper-reactivity,generation of neutrophil extracellular traps,promote the activation of the coagulation cascade in an infection-dependent manner.^(1)
基金the Intramural Research Programs of the National Institute of Neurological Disorders(ZIA-NS002263)Stroke and the National Institute on Drug Abuse(Z1A DA000609).
文摘Three recent articles published in Cell1,2 and Cell Research3 have reported multiple cryo-electron microscopy(cryo-EM)structures of the D1 dopamine receptor(DRD1)bound to either dopamine,various DRD1 agonists,or a positive allosteric modulator(PAM),while in complex with the active heterotrimeric Gs protein.These studies describe for the first time active-state structures of the DRD1,an exciting advancement in the field that will allow for a better understanding of selective agonist binding,DRD1 activation,G protein selectivity,and the provision of multiple templates to facilitate future drug design and discovery for this important therapeutic target.
