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https://www.readbyqxmd.com/read/29222784/methods-for-quantitative-analysis-of-axonal-cargo-transport
#1
Matias Alloatti, Luciana Bruno, Tomas L Falzone
Neurons rely on complex axonal transport mechanisms that mediate the intracellular dynamics of proteins, vesicles, and mitochondria along their high polarized structure. The fast improvement of live imaging techniques of fluorescent cargos allowed the identification of the diverse motion properties of different transported molecules. These properties arise as the result of molecular interactions between many players involved in axonal transport. Motor proteins, microtubule tracks, cargo association, and even axonal viscosity contribute to the proper axonal dynamics of different cargos...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29216315/the-pul37-tegument-protein-guides-alpha-herpesvirus-retrograde-axonal-transport-to-promote-neuroinvasion
#2
Alexsia L Richards, Patricia J Sollars, Jared D Pitts, Austin M Stults, Ekaterina E Heldwein, Gary E Pickard, Gregory A Smith
A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination of infection to sensory and autonomic ganglia of the peripheral nervous system following an initial exposure at mucosal surfaces. The peripheral ganglia serve as the latent virus reservoir and the source of recurrent infections such as cold sores (herpes simplex virus type I) and shingles (varicella zoster virus). However, the means by which these viruses routinely invade the nervous system is not fully understood. We report that an internal virion component, the pUL37 tegument protein, has a surface region that is an essential neuroinvasion effector...
December 7, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29207487/diffuse-axonal-injury-and-oxidative-stress-a-comprehensive-review
#3
REVIEW
Alessandro Frati, Daniela Cerretani, Anna Ida Fiaschi, Paola Frati, Vittorio Gatto, Raffaele La Russa, Alessandro Pesce, Enrica Pinchi, Alessandro Santurro, Flavia Fraschetti, Vittorio Fineschi
Traumatic brain injury (TBI) is one of the world's leading causes of morbidity and mortality among young individuals. TBI applies powerful rotational and translational forces to the brain parenchyma, which results in a traumatic diffuse axonal injury (DAI) responsible for brain swelling and neuronal death. Following TBI, axonal degeneration has been identified as a progressive process that starts with disrupted axonal transport causing axonal swelling, followed by secondary axonal disconnection and Wallerian degeneration...
December 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29198755/differentiation-between-oppositely-oriented-microtubules-controls-polarized-neuronal-transport
#4
Roderick P Tas, Anaël Chazeau, Bas M C Cloin, Maaike L A Lambers, Casper C Hoogenraad, Lukas C Kapitein
Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations, stability, and modifications. Nanometric tracking of motors to super-resolve microtubules and determine their polarity revealed that in dendrites, stable and acetylated microtubules are mostly oriented minus-end out, while dynamic and tyrosinated microtubules are oriented oppositely...
November 28, 2017: Neuron
https://www.readbyqxmd.com/read/29197621/inhibition-of-histone-deacetylase-6-hdac6-protects-against-vincristine-induced-peripheral-neuropathies-and-inhibits-tumor-growth
#5
Lawrence Van Helleputte, Mandy Kater, Dana P Cook, Caroline Eykens, Elisabeth Rossaert, Wanda Haeck, Tom Jaspers, Natasja Geens, Pieter Vanden Berghe, Conny Gysemans, Chantal Mathieu, Wim Robberecht, Philip Van Damme, Guido Cavaletti, Matthew Jarpe, Ludo Van Den Bosch
As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation and pain reduction rather than prevention of the neuropathy...
November 29, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29190027/anterograde-tract-tracing-for-assaying-axonopathy-and-transport-deficits-in-glaucoma
#6
Samuel D Crish, Brett R Schofield
Whether to stage degeneration or investigate early pathology in glaucoma, examination of axonal structure and function is essential. There are a wide variety of methods available to investigators using animal models of glaucoma, with varying utilities depending on the questions asked. Here, we describe the use of anterograde neuronal tract tracing using cholera toxin B (CTB) for the determination of axon transport integrity of the retinofugal projection. This method reveals the structure of the retinal axons as well as the functional integrity of anterograde transport systems...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29189775/visualizing-endocytic-recycling-and-trafficking-in-live-neurons-by-subdiffractional-tracking-of-internalized-molecules
#7
Merja Joensuu, Ramon Martínez-Mármol, Pranesh Padmanabhan, Nick R Glass, Nela Durisic, Matthew Pelekanos, Mahdie Mollazade, Giuseppe Balistreri, Rumelo Amor, Justin J Cooper-White, Geoffrey J Goodhill, Frédéric A Meunier
Our understanding of endocytic pathway dynamics is restricted by the diffraction limit of light microscopy. Although super-resolution techniques can overcome this issue, highly crowded cellular environments, such as nerve terminals, can also dramatically limit the tracking of multiple endocytic vesicles such as synaptic vesicles (SVs), which in turn restricts the analytical dissection of their discrete diffusional and transport states. We recently introduced a pulse-chase technique for subdiffractional tracking of internalized molecules (sdTIM) that allows the visualization of fluorescently tagged molecules trapped in individual signaling endosomes and SVs in presynapses or axons with 30- to 50-nm localization precision...
December 2017: Nature Protocols
https://www.readbyqxmd.com/read/29182149/multi-scale-multi-modal-analysis-uncovers-complex-relationship-at-the-brain-tissue-implant-neural-interface-new-emphasis-on-the-biological-interface
#8
Nicholas J Michelson, Alberto L Vazquez, James R Eles, Joseph William Salatino, Erin K Purcell, Jordan John Williams, Tracy Cui, Takashi D Yoshida Kozai
Implantable neural electrode devices are important tools for neuroscience research and have an increasing range of clinical applications. However, the intricacies of the biological response after implantation, and their ultimate impact on recording performance, remain challenging to elucidate. Establishing a relationship between the neurobiology and chronic recording performance is confounded by technical challenges related to traditional electrophysiological, material, and histological limitations. This can greatly impact the interpretations of results pertaining to device performance and tissue health surrounding the implant...
November 28, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/29180624/alpha-synuclein-facilitates-to-form-short-unconventional-microtubules-that-have-a-unique-function-in-the-axonal-transport
#9
Shiori Toba, Mingyue Jin, Masami Yamada, Kanako Kumamoto, Sakiko Matsumoto, Takuo Yasunaga, Yuko Fukunaga, Atsuo Miyazawa, Sakiko Fujita, Kyoko Itoh, Shinji Fushiki, Hiroaki Kojima, Hideki Wanibuchi, Yoshiyuki Arai, Takeharu Nagai, Shinji Hirotsune
Although α-synuclein (αSyn) has been linked to Parkinson's disease (PD), the mechanisms underlying the causative role in PD remain unclear. We previously proposed a model for a transportable microtubule (tMT), in which dynein is anchored to a short tMT by LIS1 followed by the kinesin-dependent anterograde transport; however the mechanisms that produce tMTs have not been determined. Our in vitro investigations of microtubule (MT) dynamics revealed that αSyn facilitates the formation of short MTs and preferentially binds to MTs carrying 14 protofilaments (pfs)...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29178177/cargo-crowding-at-actin-rich-regions-along-axons-causes-local-traffic-jams
#10
Parul Sood, Kausalya Murthy, T Vinod Kumar, Michael L Nonet, Gautam I Menon, Sandhya P Koushika
Steady axonal cargo flow is central to the functioning of healthy neurons. However, a substantial fraction of cargo in axons remains stationary up to several minutes (Kang, Tian et al. 2008, Tang, Scott et al. 2012, Tang, Scott et al. 2013, Iacobucci, Rahman et al. 2014). We examine the transport of precursors of synaptic vesicles (pre-SVs), endosomes and mitochondria in C. elegans touch receptor neurons (TRNs), showing that stationary cargo are predominantly present at actin-rich regions along the neuronal process...
November 27, 2017: Traffic
https://www.readbyqxmd.com/read/29176602/identification-of-dmttll5-as-a-major-tubulin-glutamylase-in-the-drosophila-nervous-system
#11
Isabelle Devambez, Juliette van Dijk, Salim Benlefki, Sophie Layalle, Yves Grau, Krzysztof Rogowski, Marie-Laure Parmentier, Laurent Soustelle
Microtubules (MTs) play crucial roles during neuronal life. They are formed by heterodimers of alpha and beta-tubulins, which are subjected to several post-translational modifications (PTMs). Amongst them, glutamylation consists in the reversible addition of a variable number of glutamate residues to the C-terminal tails of tubulins. Glutamylation is the most abundant MT PTM in the mammalian adult brain, suggesting that it plays an important role in the nervous system (NS). Here, we show that the previously uncharacterized CG31108 gene encodes an alpha-tubulin glutamylase acting in the Drosophila NS...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29172009/epo-releasing-neural-precursor-cells-promote-axonal-regeneration-and-recovery-of-function-in-spinal-cord-traumatic-injury
#12
S Carelli, T Giallongo, Z Gombalova, D Merli, A M Di Giulio, A Gorio
BACKGROUND: Spinal cord injury (SCI) is a debilitating condition characterized by a complex of neurological dysfunctions ranging from loss of sensation to partial or complete limb paralysis. Recently, we reported that intravenous administration of neural precursors physiologically releasing erythropoietin (namely Er-NPCs) enhances functional recovery in animals following contusive spinal cord injury through the counteraction of secondary degeneration. Er-NPCs reached and accumulated at the lesion edges, where they survived throughout the prolonged period of observation and differentiated mostly into cholinergic neuron-like cells...
2017: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/29170631/histamine-h3-heteroreceptors-suppress-glutamatergic-and-gabaergic-synaptic-transmission-in-the-rat-insular-cortex
#13
Hiroki Takei, Kiyofumi Yamamoto, Yong-Chul Bae, Tetsuo Shirakawa, Masayuki Kobayashi
Histamine H3 receptors are autoreceptors that regulate histamine release from histaminergic neuronal terminals. The cerebral cortex, including the insular cortex (IC), expresses abundant H3 receptors; however, the functions and mechanisms of H3 receptors remain unknown. The aim of this study was to elucidate the functional roles of H3 in synaptic transmission in layer V of the rat IC. Unitary excitatory and inhibitory postsynaptic currents (uEPSCs and uIPSCs) were obtained through paired whole-cell patch-clamp recording in cerebrocortical slice preparations...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/29163407/a-therapeutic-antiviral-antibody-inhibits-the-anterograde-directed-neuron-to-cell-spread-of-herpes-simplex-virus-and-protects-against-ocular-disease
#14
Dirk Bauer, Mira Alt, Miriam Dirks, Anna Buch, Christiane S Heilingloh, Ulf Dittmer, Bernd Giebel, André Görgens, Vivien Palapys, Maren Kasper, Anna M Eis-Hübinger, Beate Sodeik, Arnd Heiligenhaus, Michael Roggendorf, Adalbert Krawczyk
Herpes simplex virus (HSV) is a leading cause of blindness and viral encephalitis in the developed world. Upon reactivation from sensory neurons, HSV returns via axonal transport to peripheral tissues where it causes, e.g., severe, potentially blinding ocular diseases. In the present study we investigated whether the HSV-1/2 glycoprotein B-specific antibody mAb 2c or its humanized counterpart mAb hu2c can protect from ocular disease in a mouse model of HSV-1-induced acute retinal necrosis (ARN). In this model the viral spread from the initially infected to the contralateral eye resembles the routes taken in humans upon HSV reactivation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29159770/jip3-localises-to-exocytic-vesicles-and-focal-adhesions-in-the-growth-cones-of-differentiated-pc12-cells
#15
Patrick T Caswell, Martin Dickens
The JNK-interacting protein 3 (JIP3) is a molecular scaffold, expressed predominantly in neurons, that serves to coordinate the activation of the c-Jun N-terminal kinase (JNK) by binding to JNK and the upstream kinases involved in its activation. The JNK pathway is involved in the regulation of many cellular processes including the control of cell survival, cell death and differentiation. JIP3 also associates with microtubule motor proteins such as kinesin and dynein and is likely an adapter protein involved in the tethering of vesicular cargoes to the motors involved in axonal transport in neurons...
November 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29155749/immobilization-of-caenorhabditis-elegans-to-analyze-intracellular-transport-in-neurons
#16
Shinsuke Niwa
Axonal transport and intraflagellar transport (IFT) are essential for axon and cilia morphogenesis and function. Kinesin superfamily proteins and dynein are molecular motors that regulate anterograde and retrograde transport, respectively. These motors use microtubule networks as rails. Caenorhabditis elegans (C. elegans) is a powerful model organism to study axonal transport and IFT in vivo. Here, I describe a protocol to observe axonal transport and IFT in living C. elegans. Transported cargo can be visualized by tagging cargo proteins using fluorescent proteins such as green fluorescent protein (GFP)...
October 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29154141/novel-genes-associated-with-amyotrophic-lateral-sclerosis-diagnostic-and-clinical-implications
#17
REVIEW
Ruth Chia, Adriano Chiò, Bryan J Traynor
BACKGROUND: The disease course of amyotrophic lateral sclerosis (ALS) is rapid and, because its pathophysiology is unclear, few effective treatments are available. Genetic research aims to understand the underlying mechanisms of ALS and identify potential therapeutic targets. The first gene associated with ALS was SOD1, identified in 1993 and, by early 2014, more than 20 genes had been identified as causative of, or highly associated with, ALS. These genetic discoveries have identified key disease pathways that are therapeutically testable and could potentially lead to the development of better treatments for people with ALS...
November 16, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/29145394/unc-16-jip3-regulates-early-events-in-synaptic-vesicle-protein-trafficking-via-lrk-1-lrrk2-and-ap-complexes
#18
Bikash Choudhary, Madhushree Kamak, Neena Ratnakaran, Jitendra Kumar, Anjali Awasthi, Chun Li, Ken Nguyen, Kunihiro Matsumoto, Naoki Hisamoto, Sandhya P Koushika
JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the μ-subunit of the AP-1 complex...
November 16, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29134730/role-of-central-versus-peripheral-opioid-system-in-antinociceptive-and-anti-inflammatory-effect-of-botulinum-toxin-type-a-in-trigeminal-region
#19
V Drinovac Vlah, B Filipović, L Bach-Rojecky, Z Lacković
BACKGROUND: Although botulinum toxin type A (BT-A) is approved for chronic migraine treatment, its site and mechanism of action are still elusive. Recently our group discovered that suppression of CGRP release from dural nerve endings might account for antimigraine action of pericranially injected BT-A. We demonstrated that central antinociceptive effect of BT-A in sciatic region involves endogenous opioid system as well. Here we investigated possible interaction of BT-A with endogenous opioid system within the trigeminal region...
November 13, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29132416/distinct-functional-consequences-of-ecel1-dine-missense-mutations-in-the-pathogenesis-of-congenital-contracture-disorders
#20
Kenichi Nagata, Mika Takahashi, Sumiko Kiryu-Seo, Hiroshi Kiyama, Takaomi C Saido
Endothelin-converting enzyme-like 1 (ECEL1, also termed DINE in rodents), a membrane-bound metalloprotease, has been identified as a gene responsible for distal arthrogryposis (DA). ECEL1-mutated DA is generally characterized by ocular phenotypes in addition to the congenital limb contractures that are common to all DA subtypes. Until now, the consequences of the identified pathogenic mutations have remained incompletely understood because of a lack of detailed phenotypic analyses in relevant mouse models. In this study, we generated a new knock-in mouse strain that carries an ECEL1/DINE pathogenic G607S missense mutation, based on a previous study reporting atypical DA hindlimb phenotypes in two siblings with the mutation...
November 13, 2017: Acta Neuropathologica Communications
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