Abstract:
:The frontline anti-malarial drug artemisinin and its derivatives have also been implicated in modulating multiple mammalian cellular pathways, including the recent identification of targeting γ-aminobutyric acid type A receptor (GABAAR) signaling in the pancreas. Their molecular mechanism of action, however, remains elusive. Here, we present crystal structures of gephyrin, the central organizer at inhibitory postsynapses, in complex with artesunate and artemether at 1.5-Å resolution. These artemisinins target the universal inhibitory neurotransmitter receptor-binding epitope of gephyrin, thus inhibiting critical interactions between gephyrin and glycine receptors (GlyRs) as well as GABAARs. Electrophysiological recordings reveal a significant inhibition of gephyrin-mediated neurotransmission by artemisinins. Furthermore, clustering analyses in primary neurons demonstrate a rapid inhibition and a time-dependent regulation of gephyrin and GABAAR cluster parameters. Our data not only provide a comprehensive model for artemisinin-mediated modulation of inhibitory neurotransmission but also establish artemisinins as potential lead compounds to pharmacologically interfere with this process.
journal_name
Neuronjournal_title
Neuronauthors
Kasaragod VB,Hausrat TJ,Schaefer N,Kuhn M,Christensen NR,Tessmer I,Maric HM,Madsen KL,Sotriffer C,Villmann C,Kneussel M,Schindelin Hdoi
10.1016/j.neuron.2019.01.001subject
Has Abstractpub_date
2019-02-20 00:00:00pages
673-689.e11issue
4eissn
0896-6273issn
1097-4199pii
S0896-6273(19)30002-9journal_volume
101pub_type
杂志文章相关文献
NEURON文献大全abstract::The rhodopsin regulatory protein, visual arrestin, undergoes light-dependent trafficking in mammalian and Drosophila photoreceptor cells, though the mechanisms underlying these movements are poorly understood. In Drosophila, the movement of the visual arrestin, Arr2, functions in long-term adaptation and is dependent ...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2004.06.014
更新日期:2004-07-08 00:00:00
abstract::Changes in intracellular calcium (Ca) concentration following synaptic and suprathreshold activity are mediated by a wide range of sources and contribute to the regulation of myriad neuronal functions. The development of Ca imaging techniques has dramatically increased our understanding of the complex interactions bet...
journal_title:Neuron
pub_type: 杂志文章,评审
doi:10.1016/j.neuron.2008.08.020
更新日期:2008-09-25 00:00:00
abstract::We have investigated the specification of noradrenergic neurotransmitter identity in neural crest stem cells (NCSCs). Retroviral expression of both wild-type and dominant-negative forms of the paired homeodomain transcription factor Phox2a indicates a crucial and direct role for this protein (and/or the closely relate...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)80729-1
更新日期:1999-04-01 00:00:00
abstract::The role of the target cell in neurotrophin-induced modifications of glutamatergic synaptic transmission was examined in cultured hippocampal neurons. Brain-derived neurotrophic factor (BDNF) induced rapid and persistent potentiation of evoked glutamate release when the postsynaptic neuron was glutamatergic, or excita...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)80879-x
更新日期:2000-01-01 00:00:00
abstract::Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle's contractile units. Despite the motor unit's centrality to neuromuscular physiology, no extant technology can imag...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2015.11.022
更新日期:2015-12-16 00:00:00
abstract::Olfactory receptor neurons (ORNs) are replaced and differentiate in adult animals, but differentiation in dissociated cell culture has not been demonstrated. To test whether contact with the CNS regulates maturation, neonatal rat olfactory cells were grown on a culture substrate or on CNS astrocytes. Mature ORNs, immu...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/0896-6273(92)90139-5
更新日期:1992-06-01 00:00:00
abstract::Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently described neurodegenerative disorder of older adult carriers of premutation alleles (60-200 CGG repeats) in the fragile X mental retardation gene (FMR1). It has been proposed that FXTAS is an RNA-mediated neurodegenerative disease caused by the titratio...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2007.07.021
更新日期:2007-08-16 00:00:00
abstract::Memory abilities differ greatly across individuals. To explore a source of these differences, we characterized the varied strategies people adopt during unconstrained encoding. Participants intentionally encoded object pairs during functional MRI. Principal components analysis applied to a strategy questionnaire revea...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2006.06.006
更新日期:2006-07-20 00:00:00
abstract::We measured amygdala activity in human volunteers during rapid visual presentations of fearful, happy, and neutral faces using functional magnetic resonance imaging (fMRI). The first experiment involved a fixed order of conditions both within and across runs, while the second one used a fully counterbalanced order in ...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)80219-6
更新日期:1996-11-01 00:00:00
abstract::Brain functions are based on the dynamic interaction of excitatory and inhibitory inputs. Spillover of glutamate from excitatory synapses may diffuse to and modulate nearby inhibitory synapses. By recording unitary inhibitory postsynaptic currents (uIPSCs) from cell pairs in CA1 of the hippocampus, we demonstrated tha...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(01)00298-7
更新日期:2001-05-01 00:00:00
abstract::Calcium/calmodulin-dependent protein kinase II (CaMKII) can be regulated by synaptic activity and could therefore be involved in activity-dependent control of neuronal growth. We tested whether increased CaMKII activity in postsynaptic optic tectal neurons can modify the development of retinotectal axons in Xenopus. T...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)80072-0
更新日期:1996-03-01 00:00:00
abstract::The brain must make sense of external stimuli to generate relevant behavior. We used a combination of in vivo approaches to investigate how the cerebellum processes sensory-related information. We found that the inferior olive encodes contexts of sensory-associated external cues in a graded manner, apparent in the pre...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2019.03.010
更新日期:2019-05-22 00:00:00
abstract::The alpha subunit of a voltage-sensitive sodium channel characteristic of denervated rat skeletal muscle was cloned and characterized. The cDNA encodes a 2018 amino acid protein (SkM2) that is homologous to other recently cloned sodium channels, including a tetrodotoxin (TTX)-sensitive sodium channel from rat skeletal...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/0896-6273(90)90098-z
更新日期:1990-02-01 00:00:00
abstract::Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neuronal activation. We show here that disruption of MeCP2 S421 phosph...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2011.08.022
更新日期:2011-10-06 00:00:00
abstract::Although substantial advances have been made in behavioral and pharmacological treatments for addictions, moving treatment development to the next stage may require novel ways of approaching addictions, particularly ways based on new findings regarding the neurobiological underpinnings of addictions that also assimila...
journal_title:Neuron
pub_type: 杂志文章,评审
doi:10.1016/j.neuron.2011.02.009
更新日期:2011-02-24 00:00:00
abstract::Mice lacking the EphB2 receptor tyrosine kinase display a cell-autonomous, strain-specific circling behavior that is associated with vestibular phenotypes. In mutant embryos, the contralateral inner ear efferent growth cones exhibit inappropriate pathway selection at the midline, while in mutant adults, the endolymph-...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)81174-5
更新日期:2000-05-01 00:00:00
abstract::Although the function of the autonomic nervous system (ANS) in mediating the flight-or-fight response was recognized decades ago, the crucial role of peripheral innervation in regulating cell behavior and response to the microenvironment has only recently emerged. In the hematopoietic system, the ANS regulates stem ce...
journal_title:Neuron
pub_type: 杂志文章,评审
doi:10.1016/j.neuron.2015.01.026
更新日期:2015-04-22 00:00:00
abstract::Precise apposition of presynaptic and postsynaptic domains is a fundamental property of all neuronal circuits. Experiments in vitro suggest that Neuroligins and Neurexins function as key regulatory proteins in this process. In a genetic screen, we recovered several mutant alleles of Drosophila neuroligin 1 (dnlg1) tha...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2010.05.020
更新日期:2010-06-10 00:00:00
abstract::Changes in social preference of amphibian larvae result from sustained exposure to kinship odorants. To understand the molecular and cellular mechanisms of this neuroplasticity, we investigated the effects of olfactory system activation on neurotransmitter (NT) expression in accessory olfactory bulb (AOB) interneurons...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2017.08.023
更新日期:2017-09-13 00:00:00
abstract::EPAC proteins are the guanine nucleotide exchange factors that act as the intracellular receptors for cyclic AMP. Two variants of EPAC genes including EPAC1 and EPAC2 are cloned and are widely expressed throughout the brain. But, their functions in the brain remain unknown. Here, we genetically delete EPAC1 (EPAC1(-/-...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2012.02.003
更新日期:2012-02-23 00:00:00
abstract::The adipocyte-derived hormone leptin decreases body weight in part by activating the sympathetic nervous system, resulting in increased thermogenesis and energy expenditure. We investigated hypothalamic pathways underlying leptin's effects on stimulating the sympathetic nervous system. We found that leptin activates n...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)80656-x
更新日期:1998-12-01 00:00:00
abstract::To achieve simultaneous measurement of multiple cellular events in molecularly defined groups of neurons in vivo, we designed a spectrometer-based fiber photometry system that allows for spectral unmixing of multiple fluorescence signals recorded from deep brain structures in behaving animals. Using green and red Ca2+...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2018.04.012
更新日期:2018-05-16 00:00:00
abstract::The structural basis for the synthesis of specific proteins within distinct intraneuronal compartments is unknown. We studied the distribution of poly(A) mRNA within cultured cerebrocortical neurons using high resolution in situ hybridization to identify cytoskeletal components that may anchor mRNA. After 1 day in cul...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/0896-6273(94)90213-5
更新日期:1994-03-01 00:00:00
abstract::Since the early days of research into language and the brain, word meaning was assumed to be processed in specific brain regions, which most modern neuroscientists localize to the left temporal lobe. Here we use event-related fMRI to show that action words referring to face, arm, or leg actions (e.g., to lick, pick, o...
journal_title:Neuron
pub_type: 临床试验,杂志文章
doi:10.1016/s0896-6273(03)00838-9
更新日期:2004-01-22 00:00:00
abstract::We report that EphB receptors direct unique axonal behaviors required for mapping the dorsal-ventral (D-V) retinal axis along the lateral-medial (L-M) axis of the superior colliculus (SC). EphBs are expressed in a D-V gradient, ephrin-B1 in a L-M gradient in SC, and ephrin-B3 at its midline. EphBs and ephrin-Bs are ex...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(02)00799-7
更新日期:2002-08-01 00:00:00
abstract::For the past 60 years, the central nervous system has been considered immunologically privileged. Yet results from diverse fields show clear and convincing evidence of bidirectional communication between the nervous and immune systems. ...
journal_title:Neuron
pub_type:
doi:10.1016/j.neuron.2009.09.038
更新日期:2009-10-15 00:00:00
abstract::Insulin-like growth factor I (IGF-I) is a potent regulator of oligodendrocyte development and myelination in vitro, but its effect on myelination in vivo has never been tested directly. Therefore, we examined brain growth and myelination in a transgenic mouse line that overexpresses IGF-I. By postnatal day 55, when br...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/0896-6273(93)90173-o
更新日期:1993-04-01 00:00:00
abstract::Functional magnetic resonance imaging (fMRI) was used to investigate the cerebral correlates of motor sequence memory consolidation. Participants were scanned while training on an implicit oculomotor sequence learning task and during a single testing session taking place 30 min, 5 hr, or 24 hr later. During training, ...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2008.02.008
更新日期:2008-04-24 00:00:00
abstract::The establishment of axon-dendrite polarity is fundamental for radial migration of neurons during cortex development of mammals. We demonstrate that the E3 ubiquitin ligases WW-Containing Proteins 1 and 2 (Wwp1 and Wwp2) are indispensable for proper polarization of developing neurons. We show that knockout of Wwp1 and...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2018.10.008
更新日期:2018-12-05 00:00:00
abstract::Astrocytes are complex bushy cells that serve important functions through close contacts between their processes and synapses. However, the spatial interactions and dynamics of astrocyte processes relative to synapses have proven problematic to study in adult living brain tissue. Here, we report a genetically targeted...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2018.03.003
更新日期:2018-04-04 00:00:00