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Saudi Journal of Medicine & Medical... 2022Myasthenia gravis (MG) is a rare condition caused by autoantibodies against acetylcholine receptors on postsynaptic membrane that leads to weakness of skeletal muscles.... (Review)
Review
Myasthenia gravis (MG) is a rare condition caused by autoantibodies against acetylcholine receptors on postsynaptic membrane that leads to weakness of skeletal muscles. About 7 of 10 patients with MG have thymic hyperplasia and about 1 of 10 patients have thymoma. Thymectomy has increasingly been used as a treatment modality for MG. Several observational studies have shown that thymectomy results in improvement in MG and a randomized trial has established that thymectomy leads to a better outcome in non-thymomatous generalized MG. However, thymectomy is yet controversial in some disease subtypes and there are potential concerns regarding the selection of the ideal surgical approach to achieve complete removal of the thymic tissue to achieve stable remission rates. This review highlights the role of thymectomy in non-thymomatous and thymomatous MG, the effectiveness of various thymectomy methods, postoperative myasthenic crisis, and remission after thymectomy.
PubMed: 35602390
DOI: 10.4103/sjmms.sjmms_80_22 -
Frontiers in Cellular Neuroscience 2019An increase in post-synaptic Ca conductance through activation of the ionotropic N-methyl-D-aspartate receptor (NMDAR) and concomitant structural changes are essential... (Review)
Review
An increase in post-synaptic Ca conductance through activation of the ionotropic N-methyl-D-aspartate receptor (NMDAR) and concomitant structural changes are essential for the initiation of long-term potentiation (LTP) and memory formation. Memories can be initiated by coincident events, as occurs in classical conditioning, where the NMDAR can act as a molecular coincidence detector. Binding of glutamate and glycine, together with depolarization of the postsynaptic cell membrane to remove the Mg channel pore block, results in NMDAR opening for Ca conductance. Accumulating evidence has implicated both force-from-lipids and protein tethering mechanisms for mechanosensory transduction in NMDAR, which has been demonstrated by both, membrane stretch and application of amphipathic molecules such as arachidonic acid (AA). The contribution of mechanosensitivity to memory formation and consolidation may be to increase activity of the NMDAR leading to facilitated memory formation. In this review we look back at the progress made toward understanding the physiological and pathological role of NMDA receptor channels in mechanobiology of the nervous system and consider these findings in like of their potential functional implications for memory formation. We examine recent studies identifying mechanisms of both NMDAR and other mechanosensitive channels and discuss functional implications including gain control of NMDA opening probability. Mechanobiology is a rapidly growing area of biology with many important implications for understanding form, function and pathology in the nervous system.
PubMed: 31866826
DOI: 10.3389/fncel.2019.00533 -
European Journal of Immunology Nov 2023Dendritic cells (DCs) bridge innate and adaptive immunity. Their main function is to present antigens to prime T cells and initiate and shape adaptive responses. Antigen... (Review)
Review
Dendritic cells (DCs) bridge innate and adaptive immunity. Their main function is to present antigens to prime T cells and initiate and shape adaptive responses. Antigen presentation takes place through intimate contacts between the two cells, termed immune synapses (IS). During the formation of IS, information travels towards the T-cell side to induce and tune its activation; but it also travels in reverse via engagement of membrane receptors and within extracellular vesicles transferred to the DC. Such reverse information transfer and its consequences on DC fate have been largely neglected. Here, we review the events and effects of IS-mediated antigen presentation on DCs. In addition, we discuss novel technological advancements that enable monitoring DCs interactions with T lymphocytes, the main effects of DCs undergoing productive IS (postsynaptic DCs, or psDCs), and how reverse information transfer could be harnessed to modulate immune responses for therapeutic intervention.
Topics: Immunological Synapses; Dendritic Cells; T-Lymphocytes; Antigen Presentation; Antigens
PubMed: 37598303
DOI: 10.1002/eji.202350393 -
BioRxiv : the Preprint Server For... Mar 2023Catecholamine signaling is thought to modulate cognition in an inverted-U relationship, but the mechanisms are unclear. We measured norepinephrine and dopamine release,...
Catecholamine signaling is thought to modulate cognition in an inverted-U relationship, but the mechanisms are unclear. We measured norepinephrine and dopamine release, postsynaptic calcium responses, and interactions between tonic and phasic firing modes under various stimuli and conditions. High tonic activity depleted catecholamine stores, desensitized postsynaptic responses, and decreased phasic transmission. Together this provides a clearer understanding of the inverted-U relationship, offering insights into psychiatric disorders and neurodegenerative diseases with impaired catecholamine signaling.
PubMed: 37034631
DOI: 10.1101/2023.03.30.534970 -
Current Opinion in Neurobiology Aug 2022Dysregulation of glutamatergic synapses plays an important role in the pathogenesis of neurological diseases. In addition to mediating excitatory synaptic transmission,... (Review)
Review
Dysregulation of glutamatergic synapses plays an important role in the pathogenesis of neurological diseases. In addition to mediating excitatory synaptic transmission, postsynaptic glutamate receptors interact with various membrane and intracellular proteins. They form structural and/or signaling synaptic protein complexes and thereby play diverse postsynaptic functions. Recently, several postsynaptic protein complexes have been associated with various neurological diseases and hence, have been characterized as important therapeutic targets. Moreover, novel small molecules and therapeutic peptides targeting and modulating the activities of these protein complexes have been discovered, some of which have advanced through preclinical translational research and/or clinical studies. This article describes the recent investigation of eight key protein complexes associated with the postsynaptic ionotropic and metabotropic glutamate receptors as therapeutic targets for central nervous system diseases.
Topics: Receptors, Glutamate; Receptors, Metabotropic Glutamate; Synapses; Synaptic Transmission
PubMed: 35738196
DOI: 10.1016/j.conb.2022.102585 -
Current Opinion in Cell Biology Apr 2021Clustering is a prominent feature of receptors at the plasma membrane (PM). It plays an important role in signaling. Liquid-liquid phase separation (LLPS) of proteins is... (Review)
Review
Clustering is a prominent feature of receptors at the plasma membrane (PM). It plays an important role in signaling. Liquid-liquid phase separation (LLPS) of proteins is emerging as a novel mechanism underlying the observed clustering. Receptors/transmembrane signaling proteins can be core components essential for LLPS (such as LAT or nephrin) or clients enriched at the phase-separated condensates (for example, at the postsynaptic density or at tight junctions). Condensate formation has been shown to regulate signaling in multiple ways, including by increasing protein binding avidity and by modulating the local biochemical environment. In moving forward, it is important to study protein LLPS at the PM of living cells, its interplay with other factors underlying receptor clustering, and its signaling and functional consequences.
Topics: Cell Membrane; Humans; Protein Binding; Signal Transduction
PubMed: 33461072
DOI: 10.1016/j.ceb.2020.12.006 -
Current Opinion in Neurobiology Aug 2023Postsynaptic GABAergic receptors interact with various membrane and intracellular proteins to mediate inhibitory synaptic transmission. They form structural and/or... (Review)
Review
Postsynaptic GABAergic receptors interact with various membrane and intracellular proteins to mediate inhibitory synaptic transmission. They form structural and/or signaling synaptic protein complexes that perform a variety of postsynaptic functions. In particular, the key GABAergic synaptic scaffold, gephyrin, and its interacting partners govern downstream signaling pathways that are essential for GABAergic synapse development, transmission, and plasticity. In this review, we discuss recent researches on GABAergic synaptic signaling pathways. We also outline the main outstanding issues that need to be addressed in this field and highlight the association of dysregulated GABAergic synaptic signaling with the onset of various brain disorders.
Topics: Receptors, GABA-A; Synapses; Synaptic Transmission; Carrier Proteins; Neuronal Plasticity
PubMed: 37236068
DOI: 10.1016/j.conb.2023.102728 -
Cell Reports Dec 2023Catecholamine signaling is thought to modulate cognition in an inverted-U relationship, but the mechanisms are unclear. We measured norepinephrine and dopamine release,...
Catecholamine signaling is thought to modulate cognition in an inverted-U relationship, but the mechanisms are unclear. We measured norepinephrine and dopamine release, postsynaptic calcium responses, and interactions between tonic and phasic firing modes under various stimuli and conditions. High tonic activity in vivo depleted catecholamine stores, desensitized postsynaptic responses, and decreased phasic transmission. Together, these findings provide a more complete understanding of the inverted-U relationship, offering insights into psychiatric disorders and neurodegenerative diseases with impaired catecholamine signaling.
Topics: Humans; Catecholamines; Locus Coeruleus; Norepinephrine; Dopamine; Signal Transduction
PubMed: 38100349
DOI: 10.1016/j.celrep.2023.113566 -
Cells Aug 2021AMPA receptors (AMPARs) are ionotropic glutamate receptors that play a major role in excitatory neurotransmission. AMPARs are located at both presynaptic and... (Review)
Review
AMPA receptors (AMPARs) are ionotropic glutamate receptors that play a major role in excitatory neurotransmission. AMPARs are located at both presynaptic and postsynaptic plasma membranes. A huge number of studies investigated the role of postsynaptic AMPARs in the normal and abnormal functioning of the mammalian central nervous system (CNS). These studies highlighted that changes in the functional properties or abundance of postsynaptic AMPARs are major mechanisms underlying synaptic plasticity phenomena, providing molecular explanations for the processes of learning and memory. Conversely, the role of AMPARs at presynaptic terminals is as yet poorly clarified. Accruing evidence demonstrates that presynaptic AMPARs can modulate the release of various neurotransmitters. Recent studies also suggest that presynaptic AMPARs may possess double ionotropic-metabotropic features and that they are involved in the local regulation of actin dynamics in both dendritic and axonal compartments. In addition, evidence suggests a key role of presynaptic AMPARs in axonal pathology, in regulation of pain transmission and in the physiology of the auditory system. Thus, it appears that presynaptic AMPARs play an important modulatory role in nerve terminal activity, making them attractive as novel pharmacological targets for a variety of pathological conditions.
Topics: Animals; Humans; Neurons; Pain; Receptors, AMPA; Receptors, Presynaptic; Synapses; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
PubMed: 34571906
DOI: 10.3390/cells10092260 -
Current Opinion in Insect Science Dec 2023Insects rely on their sense of smell to navigate complex environments and make decisions regarding food and reproduction. However, in natural settings, the odors that... (Review)
Review
Insects rely on their sense of smell to navigate complex environments and make decisions regarding food and reproduction. However, in natural settings, the odors that convey this information may come mixed with environmental odors that can obscure their perception. Therefore, recognizing the presence of informative odors involves generalization and discrimination processes, which can be facilitated when there is a high contrast between stimuli, or the internal representation of the odors of interest outcompetes that of concurrent ones. The first two layers of the olfactory system, which involve the detection of odorants by olfactory receptor neurons and their encoding by the first postsynaptic partners in the antennal lobe, are critical for achieving such optimal representation. In this review, we summarize evidence indicating that experience-dependent changes adjust these two levels of the olfactory system. These changes are discussed in the context of the advantages they provide for detection of informative odors.
Topics: Animals; Olfactory Pathways; Smell; Odorants; Olfactory Receptor Neurons
PubMed: 37741614
DOI: 10.1016/j.cois.2023.101117