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Neuromuscular junction proteines

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https://www.readbyqxmd.com/read/29334041/autoantibodies-to-low-density-lipoprotein-receptor-related-protein-4-in-double-seronegative-myasthenia-gravis-a-systematic-review
#1
Stephen Bacchi, Philippe Kramer, Colin Chalk
BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction in which a clinical diagnosis may be confirmed with serological testing. The most common autoantibodies used to support a diagnosis of MG are anti-acetylcholine receptor antibodies and anti-muscle-specific tyrosine kinase antibodies. In cases in which both of these autoantibodies are negative (termed double-seronegative [dSNMG]), other autoantibodies such as low-density lipoprotein receptor-related protein 4 (LRP4) may be used to aid in diagnosis...
January 2018: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
https://www.readbyqxmd.com/read/29324904/prohibitin-plays-a-critical-role-in-enterovirus-71-neuropathogenesis
#2
Issac Horng Khit Too, Isabelle Bonne, Eng Lee Tan, Justin Jang Hann Chu, Sylvie Alonso
A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29323161/lack-of-fgf18-causes-abnormal-clustering-of-motor-nerve-terminals-at-the-neuromuscular-junction-with-reduced-acetylcholine-receptor-clusters
#3
Kenyu Ito, Bisei Ohkawara, Hideki Yagi, Hiroaki Nakashima, Mikito Tsushima, Kyotaro Ota, Hiroyuki Konishi, Akio Masuda, Shiro Imagama, Hiroshi Kiyama, Naoki Ishiguro, Kinji Ohno
FGF receptor 2 is involved in the formation of the neuromuscular junction (NMJ), but its in vivo ligand remains to be determined. Laser capture microdissection of the mouse spinal motor neurons (SMNs) revealed that Fgf18 mRNA is highly expressed in SMNs in adults. Expression of Fgf18 mRNA was the highest in the spinal cord at embryonic day (E) 15.5, which gradually decreased to postnatal day 7. FGF18 protein was localized at the NMJs of the tibialis anterior muscle at E18.5 and in adults. Fgf18-/- mice at E18...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29295857/defects-in-synaptic-transmission-at-the-neuromuscular-junction-precedes-motor-deficits-in-a-tdp-43q331k-transgenic-mouse-model-of-amyotrophic-lateral-sclerosis
#4
Kirat K Chand, Kah Meng Lee, John D Lee, Hao Qiu, Emily F Willis, Nickolas A Lavidis, Massimo A Hilliard, Peter G Noakes
Transactive response DNA-binding protein-43 (TDP-43) is involved in gene regulation via the control of RNA transcription, splicing, and transport. TDP-43 is a major protein component of ubiquinated inclusions that are found in amyotrophic lateral sclerosis (ALS); however, the function of TDP-43 at the neuromuscular junction (NMJ) and its role in ALS pathogenesis is largely unknown. Here, we show that TDP-43Q331K mutation in mice resulted in impaired neurotransmission by age 3 mo, preceding deficits in motor function and motor neuron loss, which were observed from age 10 mo...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29259219/pit2-regulates-neuronal-outgrowth-through-interaction-with-microtubule-associated-protein-1b
#5
Xi-Xiang Ma, Xiangyang Li, Ping Yi, Cheng Wang, Jun Weng, Li Zhang, Xuan Xu, Hao Sun, Shenglei Feng, Kai Liu, Rui Chen, Shiyue Du, Xiao Mao, Xiaomei Zeng, Luo-Ying Zhang, Mugen Liu, Bei-Sha Tang, Xiaojuan Zhu, Shan Jin, Jing-Yu Liu
PiT2 is a member of the inorganic phosphate transporter family, and is extensively expressed in the nervous system. It was found that loop7 domain of PiT2 is not required for retroviral recognition and transport function. The exact functions of loop7 remain poorly understood. Here we show that loop7 of PiT2 is necessary for the transport of PiT2 protein to the cell surface. Further, loop7 is also related to the outgrowth of neurite in Neuro2A cells interacts with the light chain 1 of microtubule-associated protein 1B (MAP1B)...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29258853/drosophila-active-zones-from-molecules-to-behaviour
#6
REVIEW
Nadine Ehmann, David Owald, Robert J Kittel
In a constantly changing environment, neuronal circuits need to be updated and adjusted to elicit directed actions. Synaptic plasticity plays an important role in modulating such globally and locally acting networks. The active zone (AZ) is a protein-rich compartment of chemical synapses, where precisely orchestrated molecular interactions control synaptic vesicle (SV) fusion with the presynaptic membrane. The subsequent release of neurotransmitter substances onto postsynaptic receptor fields forms the basis of neuronal communication...
December 16, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29249293/epigenetic-crosstalk-pharmacological-inhibition-of-hdacs-can-rescue-defective-synaptic-morphology-and-neurotransmission-phenotypes-associated-with-loss-of-the-chromatin-reader-kismet
#7
REVIEW
Nina K Latcheva, Jennifer M Viveiros, Edward A Waddell, Phuong T T Nguyen, Faith L W Liebl, Daniel R Marenda
We are beginning to appreciate the complex mechanisms by which epigenetic proteins control chromatin dynamics to tightly regulate normal development. However, the interaction between these proteins, particularly in the context of neuronal function, remains poorly understood. Here, we demonstrate that the activity of histone deacetylases (HDACs) opposes that of a chromatin remodeling enzyme at the Drosophila neuromuscular junction (NMJ). Pharmacological inhibition of HDAC function reverses loss of function phenotypes associated with Kismet, a chromodomain helicase DNA-binding (CHD) protein...
December 14, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29247619/a-new-drosophila-model-of-ubiquilin-knockdown-shows-the-effect-of-impaired-proteostasis-on-locomotive-and-learning-abilities
#8
Salinee Jantrapirom, Luca Lo Piccolo, Hideki Yoshida, Masamitsu Yamaguchi
Ubiquilin (UBQLN) plays a crucial role in cellular proteostasis through its involvement in the ubiquitin proteasome system and autophagy. Mutations in the UBQLN2 gene have been implicated in amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal lobar dementia (ALS/FTLD). Previous studies reported a key role for UBQLN in Alzheimer's disease (AD); however, the mechanistic involvement of UBQLN in other neurodegenerative diseases remains unclear. The genome of Drosophila contains a single UBQLN homolog (dUbqn) that shows high similarity to UBQLN1 and UBQLN2; therefore, the fly is a useful model for characterizing the role of UBQLN in vivo in neurological disorders affecting locomotion and learning abilities...
December 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29230271/the-role-of-oxidative-stress-in-decreased-acetylcholinesterase-activity-at-the-neuromuscular-junction-of-the-diaphragm-during-sepsis
#9
Hua Liu, Jin Wu, Jun-Yan Yao, Hong Wang, Shi-Tong Li
Our recent study demonstrated that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm decreased during sepsis. However, the mechanisms were not clearly identified. In this study, we aimed to investigate whether the decreased AChE activity was related to oxidative stress by observing AChE activity in different grades of sepsis induced by caecal ligation and puncture (CLP). At 24 h after surgery, an assay of thiobarbituric acid reactive species (TBARS) and protein carbonyls, as well as the myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity, was conducted...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29221906/presynaptic-active-zones-of-mammalian-neuromuscular-junctions-nanoarchitecture-and-selective-impairments-in-aging
#10
REVIEW
Yomna Badawi, Hiroshi Nishimune
Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification...
December 5, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29221139/epstein-barr-virus-in-tumor-infiltrating-b-cells-of-myasthenia-gravis-thymoma-an-innocent-bystander-or-an-autoimmunity-mediator
#11
Paola Cavalcante, Stefania Marcuzzo, Sara Franzi, Barbara Galbardi, Lorenzo Maggi, Teresio Motta, Raffaella Ghislandi, Antonella Buzzi, Luisella Spinelli, Lorenzo Novellino, Fulvio Baggi, Carlo Antozzi, Fabio Conforti, Tommaso Martino De Pas, Massimo Barberis, Pia Bernasconi, Renato Mantegazza
The thymus plays a key role in myasthenia gravis (MG), a B cell-mediated autoimmune disorder affecting neuromuscular junction. Most MG patients have thymic abnormalities, including hyperplasia and thymoma, a neoplasm of thymic epithelial cells. Epstein-Barr virus (EBV) is associated with autoimmune diseases and tumors. Recently, we showed EBV persistence and reactivation in hyperplastic MG thymuses, suggesting that EBV might contribute to intra-thymic B cell dysregulation in MG patients. Here, we investigated EBV involvement in thymoma-associated MG, by searching for EBV markers in MG (n=26) and non-MG (n=14) thymomas...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217522/drosophila-syd-1-has-rhogap-activity-that-is-required-for-presynaptic-clustering-of-bruchpilot-elks-but-not-neurexin-1
#12
Michael A Spinner, David A Walla, Tory G Herman
Syd-1 proteins are required for presynaptic development in worm, fly, and mouse. Syd-1s in all three species contain a Rho GTPase activating protein (GAP)-like domain of unclear significance. Invertebrate Syd-1s are thought to lack GAP activity, and mouse mSYD1A has GAP activity that is thought to be dispensible for its function. Here we show that Drosophila melanogaster Syd-1 can interact with all six fly Rhos and has GAP activity toward Rac1 and Cdc42. During development, fly Syd-1 clusters multiple presynaptic proteins at the neuromuscular junction (NMJ), including the cell adhesion molecule Neurexin (Nrx-1) and the active zone (AZ) component Bruchpilot (Brp), both of which Syd-1 binds directly...
December 7, 2017: Genetics
https://www.readbyqxmd.com/read/29215185/potential-of-autologous-adipose-derived-stem-cells-to-regenerate-atrophied-muscle-in-a-rat-model
#13
Ji Ung Park, Sung Tack Kwon
Muscle atrophy results in severe functional impairment and is a significant clinical problem. We examined and characterized the therapeutic effects of autologous adipose-derived stem cells (ADCSs) using an in vivo muscle atrophy rat model. To identify the effect of injected ADSCs into muscle, we developed the following two models of muscle atrophy in rats: induction of denervation by sciatic nerve defects; and nerve repair after severing the sciatic nerve. The inguinal fat pads were harvested from each rat and autologous ADSCs were cultured and ADSCs were injected in the right hind limbs as the experimental group, while normal saline was injected in the left hind limbs, which served as the control group...
December 7, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29194538/mitochondrial-abnormalities-and-disruption-of-the-neuromuscular-junction-precede-the-clinical-phenotype-and-motor-neuron-loss-in-hfuswt-transgenic-mice
#14
Eva So, Jacqueline C Mitchell, Caroline Memmi, George Chennell, Gema Vizcay-Barrena, Leanne Allison, Christopher E Shaw, Caroline Vance
FUS mislocalisation and cytoplasmic aggregation are hallmark pathologies in FUS-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Many of the mechanistic hypotheses have focused on a loss of nuclear function in the FUS-opathies, implicating dysregulated RNA transcription and splicing in driving neurodegeneration. Recent studies describe an additional somato-dendritic localisation for FUS in the cerebral cortex implying a regulatory role in mRNA transport and local translation at the synapse...
November 28, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29194454/development-of-a-tissue-specific-ribosome-profiling-approach-in-drosophila-enables-genome-wide-evaluation-of-translational-adaptations
#15
Xun Chen, Dion Dickman
Recent advances in next-generation sequencing approaches have revolutionized our understanding of transcriptional expression in diverse systems. However, measurements of transcription do not necessarily reflect gene translation, the process of ultimate importance in understanding cellular function. To circumvent this limitation, biochemical tagging of ribosome subunits to isolate ribosome-associated mRNA has been developed. However, this approach, called TRAP, lacks quantitative resolution compared to a superior technology, ribosome profiling...
December 1, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29186674/cellular-and-molecular-anatomy-of-the-human-neuromuscular-junction
#16
Ross A Jones, Carl Harrison, Samantha L Eaton, Maica Llavero Hurtado, Laura C Graham, Leena Alkhammash, Oladayo A Oladiran, Andy Gale, Douglas J Lamont, Hamish Simpson, Martin W Simmen, Christian Soeller, Thomas M Wishart, Thomas H Gillingwater
The neuromuscular junction (NMJ) plays a fundamental role in transferring information from lower motor neuron to skeletal muscle to generate movement. It is also an experimentally accessible model synapse routinely studied in animal models to explore fundamental aspects of synaptic form and function. Here, we combined morphological techniques, super-resolution imaging, and proteomic profiling to reveal the detailed cellular and molecular architecture of the human NMJ. Human NMJs were significantly smaller, less complex, and more fragmented than mouse NMJs...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29168801/the-histone-code-reader-spin1-controls-skeletal-muscle-development
#17
Holger Greschik, Delphine Duteil, Nadia Messaddeq, Dominica Willmann, Laura Arrigoni, Manuela Sum, Manfred Jung, Daniel Metzger, Thomas Manke, Thomas Günther, Roland Schüle
While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1(M5) mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1(M5) mice die shortly after birth displaying severe sarcomere disorganization and necrosis. Surviving Spin1(M5) mice are growth-retarded and exhibit the most prominent defects in soleus, tibialis anterior, and diaphragm muscle...
November 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29167324/the-impact-of-spatio-temporal-calcium-dynamics-within-presynaptic-active-zones-on-synaptic-delay-at-the-frog-neuromuscular-junction
#18
Anne E Homan, Rozita Laghaei, Markus Dittrich, Stephen D Meriney
The spatio-temporal calcium dynamics within presynaptic neurotransmitter release sites (active zones, AZs) at the time of synaptic vesicle fusion is critical for neurotransmitter release. Specifically, the relative arrangement and density of voltage gated calcium channels (VGCCs) as well as the concentration of calcium buffering proteins can play a large role in the timing, magnitude and plasticity of release by shaping the AZ calcium profile. However, a high-resolution understanding of the role of AZ structure on the spatiotemporal calcium dynamics and how that may contribute to functional heterogeneity at an adult synapse is currently lacking...
November 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29166305/botulinum-toxin-therapy-is-syringe-type-related-to-cost-effectiveness
#19
Mark Anthony Foglietti, Lauren Wright, Alanna Foglietti-Fostyk
INTRODUCTION: Clostridium botulinum toxin is effective through cleaving presynaptic proteins at the neuromuscular junction, which prevents the release of acetylcholine and inhibits muscle contraction. Several serotypes of botulinum toxin (BT) exist; however, only 2 types have been approved by the US Food and Drug Administration for commercial and medical use, A and B. Both types of BT must be administered intramuscularly with a syringe, but the type of syringe is the injector's preference...
November 21, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/29162978/exploring-the-interaction-of-drosophila-tdp-43-and-the-type-ii-voltage-gated-calcium-channel-cacophony-in-regulating-motor-function-and-behavior
#20
Kayly M Lembke, David B Morton
Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neurodegenerative disease. The cause of the disease remains obscure, and as such there is no effective treatment or cure. Amyotrophic lateral sclerosis and other neurodegenerative diseases are frequently characterized by dysfunction of the RNA-binding protein, TDP-43. Using model systems to understand the mechanisms underlying TDP-43 dysfunction should accelerate identification of therapeutic targets. A recent report has shown that motor defects caused by the deletion of the Drosophila TDP-43 ortholog, tbph, are not driven by changes in the physiology at the neuromuscular junction...
2017: Journal of Experimental Neuroscience
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