Article
Biochemistry & Molecular Biology
Aleksandra Polishchuk, Victor Cilleros-Mane, Laia Just-Borras, Marta Balanya-Segura, Genis Vandellos Pont, Carolina Silvera Simon, Marta Tomas, Neus Garcia, Josep Tomas, Maria A. Lanuza
Summary: Bidirectional communication between presynaptic and postsynaptic components at the neuromuscular synapse involves retrograde regulation of ACh release through phosphorylation of SNAP-25 and Synapsin-1. Muscle contraction leads to downregulation of pSynapsin-1 S9 and upregulation of pSNAP-25 T138, resulting in decreased neurotransmitter release.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2023)
Article
Neurosciences
Kosala N. Dissanayake, Filip Margetiny, Charlotte L. Whitmore, Robert C-C Chou, Cornelia Roesl, Vishwendra Patel, Joseph J. McArdle, Richard Webster, David Beeson, John E. H. Tattersall, David J. A. Wyllie, Michael Eddleston, Richard R. Ribchester
Summary: Intentional ingestion of agricultural organophosphorus insecticides is a significant public health issue in rural Asia, leading to thousands of deaths annually. Cyclohexanol alters synaptic transmission at neuromuscular junctions, reducing postsynaptic sensitivity to acetylcholine while enhancing evoked transmitter release.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Neurosciences
Ryan J. Durbin, Dante J. Heredia, Thomas W. Gould, Robert B. Renden
Summary: Neurotransmission is influenced by extracellular pH. Alkalization enhances transmitter release and receptor activation, while acidification inhibits these processes and can activate acid-sensitive conductances in the synaptic cleft. The direction of change differs across synapse types. At the mammalian neuromuscular junction (NMJ), the direction and magnitude of pH transients in the synaptic cleft during transmission remain unclear. In this study, researchers investigated the extracellular pH transients at the cholinergic synapse of the mouse NMJ under near physiological conditions and identified their sources. They found that activity-induced intracellular Ca2+ release in the muscle plays a role in cleft alkalization, whereas PMCA inhibition decreases alkalization. This suggests that cholinergic synapses at the mouse NMJ typically alkalize due to cytosolic Ca2+ liberation during activity, unless under highly strenuous conditions where acidification predominates.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Friederike Schuemann, Oliver Schmitt, Andreas Wree, Alexander Hawlitschka
Summary: In Parkinson's disease, hypercholinism in the striatum leads to disturbed motor functions. Injecting Botulinum neurotoxin-A into the striatum of Parkinsonian rats resulted in increased immunoreactivity for cleaved SNAP-25 in brain regions other than the injected striatum, suggesting a bidirectional axonal transport of BoNT-A to connected parts of the brain. The distance from the injected striatum and the time until maximum immunoreactivity was reached showed a linear relationship.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Yifu Han, Chun Chien, Pragya Goel, Kaikai He, Cristian Pinales, Christopher Buser, Dion Dickman
Summary: In this study, the researchers used the Drosophila larval neuromuscular junction as a model system to separate neurotransmission between tonic and phasic neurons using botulinum neurotoxin BoNT-C. They also identified heterosynaptic plasticity rules in this circuit.
Article
Multidisciplinary Sciences
Mia Krout, Kelly H. Oh, Ame Xiong, Elisa B. Frankel, Peri T. Kurshan, Hongkyun Kim, Janet E. Richmond
Summary: Synaptic transmission requires the coordinated activity of multiple synaptic proteins at the active zone (AZ). CLA-1 and UNC-10 work together to regulate the levels of the UNC-2 calcium channel and the localization of UNC-13 at the synapse. These findings suggest a conserved arrangement of AZ scaffolding proteins that are crucial for precise coupling to Ca2+ channels.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Alexander Gardner, William H. Tepp, Marite Bradshaw, Joseph T. Barbieri, Sabine Pellett
Summary: This study investigated the intracellular localization of LC/A3 and LC/A1 in BoNT/A and their impact on potency, finding that the association of LC/A with the plasma membrane contributes to enhanced toxin activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Alejandra Navarro-Martinez, Cristina Vicente-Garcia, Jaime J. Carvajal
Summary: Neuromuscular junctions (NMJs) are specialized chemical synapses that transmit electrical stimuli from motor neurons to skeletal muscle. Disorders in NMJs can be caused by mutations in proteins located in the NMJ. This review highlights potential candidate genes for NMJ-related pathologies in humans by studying mouse models. It also emphasizes the importance of choosing an appropriate model organism to study NMJ-related diseases, as NMJs can vary between species, muscles, or sexes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Neurosciences
Alex Dyson, Megan Ryan, Shruti Garg, Gareth Evans, Richard A. Baines
Summary: This study investigates the relationship between neurofibromatosis type 1 (NF1) and autism spectrum disorder (ASD) using a Drosophila model. It shows that loss of function of the NF1 gene in flies leads to tactile hypersensitivity and synaptic transmission deficits, resembling sensory abnormalities seen in individuals with ASD. The study suggests that NF1 deficiency may cause neuronal hyperexcitability and that decreased NF1 expression results in excessive neuronal firing and tactile hypersensitivity, potentially linking these two aspects. Knock-down of Ras proteins rescues both synaptic transmission deficits and behavioral deficits.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Food Science & Technology
Flavia Antonucci, Yuri Bozzi
Summary: Botulinum neurotoxins (BoNTs) are zinc endopeptidases that can inhibit the release of neurotransmitters, potentially providing therapeutic effects in certain neurological disorders. However, their efficacy is limited in humans.
Article
Biology
Tianzhi Li, Qiqi Cheng, Shen Wang, Cong Ma
Summary: Exocytosis of secretory vesicles relies on the interaction between Rabphilin 3A and SNAP-25, which promotes SNARE complex assembly and vesicle docking and fusion with the plasma membrane. This interaction is mediated by the N-terminal Rab-binding domain and C-terminal C(2)AB domain of Rabphilin 3A, as well as the C2B bottom alpha-helix of Rabphilin 3A and the N-peptide region of SNAP-25.
Article
Biochemistry & Molecular Biology
V Cilleros-Mane, L. Just-Borras, A. Polishchuk, M. Duran, M. Tomas, N. Garcia, J. M. Tomas, M. A. Lanuza
Summary: The study reveals how M-1 and M-2 mAChR regulate PKC beta I and epsilon isoforms, influencing the mechanism of neurotransmitter release. M-1 activates PDK1 to promote phosphorylation of PKC beta I and epsilon, while M-2 inhibits the synthesis of PKC epsilon through a PKA-dependent pathway.
Review
Biochemistry & Molecular Biology
Pragya Goel, Dion Dickman
Summary: Homeostatic signaling systems play a crucial role in maintaining stable functionality in changing environments by regulating the balance of excitation and inhibition at synapses. Research on the Drosophila neuromuscular junction has identified five homeostats that work independently yet simultaneously to balance neurotransmission. These ancient signaling systems are believed to have emerged early in evolution and play a fundamental role in stabilizing mammalian cholinergic NMJs and glutamatergic central synapses.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Neurosciences
Guangming Gan, Mei Chen, Qinfeng Yu, Xiang Gao, Chenchen Zhang, Qingyuan Sheng, Wei Xie, Junhua Geng
Summary: This study uses transmission electron microscopy to observe the degeneration process of the larval neuromuscular junction (NMJ) in Drosophila. The subsynaptic reticulum (SSR) swells and retracts before degenerating into a disordered membrane. The axon terminal and synaptic vesicles also undergo degeneration. The study suggests that neurexin and neuroligins play crucial roles in preventing synaptic degeneration in Drosophila.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Sydney V. Doss, Sebastien Barbat-Artigas, Mikayla Lopes, Bhola Shankar Pradhan, Tomasz J. Proszynski, Richard Robitaille, Gregorio Valdez
Summary: Lynx1 is expressed in skeletal muscles and concentrates at NMJs. It interacts with muscle-specific nAChR subunits and affects the response of skeletal muscles to cholinergic transmission and their contractile properties. Loss of Lynx1 has a minor role in the structural development of NMJs and may primarily function to maintain the structure and function of adult and aging NMJs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Sunaina Surana, David Villarroel-Campos, Oscar M. Lazo, Edoardo Moretto, Andrew P. Tosolini, Elena R. Rhymes, Sandy Richter, James N. Sleigh, Giampietro Schiavo
Article
Biochemistry & Molecular Biology
Alexander D. Fellows, Elena R. Rhymes, Katherine L. Gibbs, Linda Greensmith, Giampietro Schiavo
Article
Cell Biology
Marta Budzinska, David Villarroel-Campos, Matthew Golding, Anne Weston, Lucy Collinson, Ambrosius P. Snijders, Giampietro Schiavo
JOURNAL OF CELL SCIENCE
(2020)
Article
Neurosciences
Alexander M. Rossor, James N. Sleigh, Michael Groves, Francesco Muntoni, Mary M. Reilly, Casper C. Hoogenraad, Giampietro Schiavo
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2020)
Article
Anatomy & Morphology
Aleksandra M. Mech, Anna-Leigh Brown, Giampietro Schiavo, James N. Sleigh
JOURNAL OF ANATOMY
(2020)
Review
Biochemistry & Molecular Biology
Samantha De La-Rocque, Edoardo Moretto, Ioana Butnaru, Giampietro Schiavo
Summary: The presence and distribution of tau in the brain of AD patients are closely related to cognitive decline, more so than amyloid plaque deposition. Tau pathology can spread within the central nervous system via a prion-like mechanism, showing a stereotypical pattern and involving trans-synaptic inter-neuronal transfer.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Neurosciences
James N. Sleigh, Aleksandra M. Mech, Tahmina Aktar, Yuxin Zhang, Giampietro Schiavo
FRONTIERS IN CELLULAR NEUROSCIENCE
(2020)
Article
Cell Biology
James N. Sleigh, Aleksandra M. Mech, Giampietro Schiavo
CELL DEATH & DISEASE
(2020)
Review
Biochemistry & Molecular Biology
Reem Abouward, Giampietro Schiavo
Summary: Localisation of mRNA plays a crucial role in establishing and maintaining cellular polarity, synaptic plasticity, and other biological processes. Recent discoveries regarding RNA hitchhiking on cytoplasmic organelles have significant implications on our understanding of neuronal function in development, adulthood, and neurodegeneration. The mechanisms controlling mRNA localisation are largely conserved across evolution and have been extensively studied in various biological models.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Anatomy & Morphology
David Villarroel-Campos, Giampietro Schiavo, James N. Sleigh
Summary: Analysis of rodent muscles can provide insights into neuromuscular development and disease-causing genetic mutations. Studies commonly use distal leg muscles, but thin and flat muscles like the epitrochleoanconeus in the upper forelimb are more suitable for detailed peripheral motor nervous system analysis. The method described in this study allows rapid isolation of the epitrochleoanconeus within five minutes, facilitating its incorporation into neuromuscular disease research.
JOURNAL OF ANATOMY
(2022)
Article
Cell Biology
Elena R. Rhymes, Andrew P. Tosolini, Alexander D. Fellows, William Mahy, Neil Q. McDonald, Giampietro Schiavo
Summary: This study investigates the interplay between the tyrosine kinase receptor RET for glial cell line-derived neurotrophic factor (GDNF) and axonal transport in neurons. By blocking RET signaling using inhibitors and genetic knockdown, the study demonstrates enhanced signaling endosome transport and rescue of axonal transport deficits in both wild-type and SOD1(G93A) motor neurons. These findings suggest RET as a potential therapeutic target for ALS treatment.
CELL DEATH & DISEASE
(2022)
Article
Neurosciences
Andrew P. Tosolini, James N. Sleigh, Sunaina Surana, Elena R. Rhymes, Stephen D. Cahalan, Giampietro Schiavo
Summary: Axonal transport is essential for neuronal development, function, and survival. In ALS, fast motor neurons degenerate first while slow motor neurons are more resistant. The study investigates the effects of BDNF on axonal transport in different subtypes of motor neurons, and identifies impaired BDNF signaling as a key deficit in ALS.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biology
Oscar Marcelo Lazo, Giampietro Schiavo
Summary: Neurons process real-time information by encoding inputs from distal axons as a stream of endocytic organelles, called signalling endosomes, targeted to the soma. The sorting mechanism of TrkB to signalling endosomes is unknown. In this study, we identify Rab10 as critical for TrkB sorting and propagation of BDNF signalling from axon terminals to the soma, providing insights into neurodegenerative diseases.
Article
Cell Biology
Ana del Puerto, Coral Lopez-Fonseca, Ana Simon-Garcia, Beatriz Marti-Prado, Ana L. L. Barrios-Munoz, Julia Pose-Utrilla, Celia Lopez-Menendez, Berta Alcover-Sanchez, Fabrizia Cesca, Giampietro Schiavo, Miguel R. R. Campanero, Isabel Farinas, Teresa Iglesias, Eva Porlan
Summary: In the adult mammalian brain, neural stem cells (NSCs) play a crucial role in generating new neurons and integrating them into existing circuits. The regulation of NSCs activation and survival is important for normal brain function and has implications for aging, neurodegeneration, and glioma. This study identifies Kidins220 as a key regulator of NSCs activation and survival, showing that it acts through AKT-GSK3 signaling pathway and can modulate the NSCs response to growth factors.
CELL DEATH & DISEASE
(2023)
Article
Biology
James N. Sleigh, Steven J. West, Giampietro Schiavo
BMC RESEARCH NOTES
(2020)
Article
Pharmacology & Pharmacy
Mohammadhossein Movassaghghazani, Nazanin Shabansalmani
Summary: The study revealed high levels of AFM1 in both breast milk and powdered milk samples in Tehran, with some samples exceeding the established limits. Therefore, monitoring and regulating toxin levels in these products is crucial for maternal and infant health.
Article
Pharmacology & Pharmacy
Defeng Wen, Wantong Han, Quan Chen, Guanhui Qi, Mengling Gao, Pu Guo, Yu Liu, Zhongyuan Wu, Shulin Fu, Qirong Lu, Yinsheng Qiu
Summary: Luteolin can inhibit FB1-induced intestinal inflammatory injury by inhibiting the activation of NF-kappa B and ERK signaling pathways, according to network pharmacology and in vitro experiments.