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https://www.readbyqxmd.com/read/29447116/amyloid-toxicity-in-alzheimer-s-disease
#1
REVIEW
Allison B Reiss, Hirra A Arain, Mark M Stecker, Nicolle M Siegart, Lora J Kasselman
A major feature of Alzheimer's disease (AD) pathology is the plaque composed of aggregated amyloid-β (Aβ) peptide. Although these plaques may have harmful properties, there is much evidence to implicate soluble oligomeric Aβ as the primary noxious form. Aβ oligomers can be generated both extracellularly and intracellularly. Aβ is toxic to neurons in a myriad of ways. It can cause pore formation resulting in the leakage of ions, disruption of cellular calcium balance, and loss of membrane potential. It can promote apoptosis, cause synaptic loss, and disrupt the cytoskeleton...
February 15, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29446228/integrins-promote-axonal-regeneration-after-injury-of-the-nervous-system
#2
Bart Nieuwenhuis, Barbara Haenzi, Melissa R Andrews, Joost Verhaagen, James W Fawcett
Integrins are cell surface receptors that form the link between extracellular matrix molecules of the cell environment and internal cell signalling and the cytoskeleton. They are involved in several processes, e.g. adhesion and migration during development and repair. This review focuses on the role of integrins in axonal regeneration. Integrins participate in spontaneous axonal regeneration in the peripheral nervous system through binding to various ligands that either inhibit or enhance their activation and signalling...
February 15, 2018: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29438303/cytoskeletons-in-the-closet-subversion-in-alphaherpesvirus-infections
#3
REVIEW
Christopher E Denes, Monica Miranda-Saksena, Anthony L Cunningham, Russell J Diefenbach
Actin filaments, microtubules and intermediate filaments form the cytoskeleton of vertebrate cells. Involved in maintaining cell integrity and structure, facilitating cargo and vesicle transport, remodelling surface structures and motility, the cytoskeleton is necessary for the successful life of a cell. Because of the broad range of functions these filaments are involved in, they are common targets for viral pathogens, including the alphaherpesviruses. Human-tropic alphaherpesviruses are prevalent pathogens carried by more than half of the world's population; comprising herpes simplex virus (types 1 and 2) and varicella-zoster virus, these viruses are characterised by their ability to establish latency in sensory neurons...
February 13, 2018: Viruses
https://www.readbyqxmd.com/read/29437244/epothilone-d-correct-drug-wrong-disease
#4
EDITORIAL
Yazi D Ke, Lars M Ittner
Changes to the neuronal cytoskeleton, and in particular to microtubules, have been implicated in a wide range of neurodegenerative diseases, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). As such, there are growing reports of microtubules-modulating drugs used to treat neurodegeneration in mice. For example, long-term treatment of a mutant tau transgenic mouse model of FTD and AD with low doses of the cancer drug Epothilone D (EpoD), a microtubule stabilizing compound, reduced cognitive deficits in young animals [1] and improved neuropathology in aged animals [2], without overt side effects...
February 13, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29429047/the-small-gtpase-rac1-ced-10-is-essential-in-maintaining-dopaminergic-neuron-function-and-survival-against-%C3%AE-synuclein-induced-toxicity
#5
Hanna Kim, Carles Calatayud, Sangib Guha, Irene Fernández-Carasa, Laura Berkowitz, Iria Carballo-Carbajal, Mario Ezquerra, Rubén Fernández-Santiago, Pankaj Kapahi, Ángel Raya, Antonio Miranda-Vizuete, Jose Miguel Lizcano, Miquel Vila, Kim A Caldwell, Guy A Caldwell, Antonella Consiglio, Esther Dalfo
Parkinson's disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to the organization of the actin and microtubule cytoskeletons, has been suggested to participate to Parkinson's disease pathogenesis. Nevertheless, its exact contribution remains obscure. To unveil the participation of the Rho GTPase family to the molecular pathogenesis of Parkinson's disease, we first used C elegans to demonstrate the role of the small GTPase RAC1 (ced-10 in the worm) in maintaining dopaminergic function and survival in the presence of alpha-synuclein...
February 10, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29410983/nanotopography-regulates-motor-neuron-differentiation-of-human-pluripotent-stem-cells
#6
Weiqiang Chen, Shuo Han, Weiyi Qian, Shinuo Weng, Haiou Yang, Yubing Sun, Luis G Villa-Diaz, Paul H Krebsbach, Jianping Fu
The regulation of human pluripotent stem cell (hPSC) behaviors has been mainly studied through exploration of biochemical factors. However, the current directed differentiation protocols for hPSCs that completely rely on biochemical factors remain suboptimal. It has recently become evident that coexisting biophysical signals in the stem cell microenvironment, including nanotopographic cues, can provide potent regulatory signals to mediate adult stem cell behaviors, including self-renewal and differentiation...
February 7, 2018: Nanoscale
https://www.readbyqxmd.com/read/29408940/regulation-of-neuritogenesis-in-hippocampal-neurons-using-stiffness-of-extracellular-microenvironment
#7
Aya Tanaka, Yuki Fujii, Nahoko Kasai, Takaharu Okajima, Hiroshi Nakashima
The mechanosensitivity of neurons in the central nervous system (CNS) is an interesting issue as regards understanding neuronal development and designing compliant materials as neural interfaces between neurons and external devices for treating CNS injuries and disorders. Although neurite initiation from a cell body is known to be the first step towards forming a functional nervous network during development or regeneration, less is known about how the mechanical properties of the extracellular microenvironment affect neuritogenesis...
2018: PloS One
https://www.readbyqxmd.com/read/29408692/proteomic-analysis-of-the-sarcolemma-enriched-fraction-from-dystrophic-mdx-4cv-skeletal-muscle
#8
Sandra Murphy, Margit Zweyer, Michael Henry, Paula Meleady, Rustam R Mundegar, Dieter Swandulla, Kay Ohlendieck
The highly progressive neuromuscular disorder dystrophinopathy is triggered by primary abnormalities in the Dmd gene, which causes cytoskeletal instability and loss of sarcolemmal integrity. Comparative organellar proteomics was employed to identify sarcolemma-associated proteins with an altered concentration in dystrophic muscle tissue from the mdx-4cv mouse model of dystrophinopathy. A lectin agglutination method was used to prepare a sarcolemma-enriched fraction and resulted in the identification of 190 significantly changed protein species...
February 1, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29395317/dystrophin-71-and-%C3%AE-1syntrophin-in-morpho-functional-plasticity-of-rat-supraoptic-nuclei-effect-of-saline-surcharge-and-reversibly-normal-hydration
#9
Madina Sifi, Roza Benabdesselam, Sabrina Souttou, Tiziana Annese, Alvaro Rendon, Beatrice Nico, Latifa Dorbani-Mamine
Dystrophin (Dp) is a multidomain protein that links the actin cytoskeleton to the extracellular matrix through the dystrophin associated proteins complex (DAPC). Dp of 71 kDa (Dp71), corresponding to the COOH-terminal domain of dystrophin, and α1-syntrophin (α1Syn) as the principal component of the DAPC, are strongly expressed in the brain. To clarify their involvement in the central control of osmotic homeostasis, we investigated the effect of 14 days of salt loading (with drinking water containing 2% NaCl) and then reversibly to 30 days of normal hydration (with drinking water without salt), first on the expression by western-blotting and the distribution by immunochemistry of Dp71 and α1Syn in the SON of the rat and, second, on the level of some physiological parameters, as the plasma osmolality, natremia and hematocrit...
January 26, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29394500/mutations-in-mical-1-cause-autosomal-dominant-lateral-temporal-epilepsy
#10
Emanuela Dazzo, Kati Rehberg, Roberto Michelucci, Daniela Passarelli, Clementina Boniver, Valeria Vianello Dri, Pasquale Striano, Salvatore Striano, R Jeroen Pasterkamp, Carlo Nobile
OBJECTIVE: Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy characterized by auditory symptoms. Two genes, LGI1 and RELN, encoding secreted proteins, are implicated in the etiology of ADLTE, but half of the affected families remain genetically unsolved, and the underlying molecular mechanisms are yet to be clarified. We aimed to identify additional genes causing ADLTE to better understand the genetic basis and molecular pathway underlying this epileptic disorder...
February 2, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29382806/same-but-different-pleiotropy-in-centrosome-related-microcephaly
#11
Ryan S O'Neill, Todd A Schoborg, Nasser M Rusan
An intimate link between centrosome function and neurogenesis is revealed by the identification of many genes with centrosome-associated functions that are mutated in microcephaly disorders. Consistent with the major role of the centrosome in mitosis, mutations in these centrosome-related microcephaly (CRM) genes are thought to affect neurogenesis by depleting the pool of neural progenitor cells, primarily through apoptosis as a consequence of mitotic failure or premature differentiation as a consequence of cell cycle delay and randomization of spindle orientation...
February 1, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29382228/primary-fibroblasts-derived-from-sporadic-amyotrophic-lateral-sclerosis-patients-do-not-show-als-cytological-lesions
#12
Philippe Codron, Julien Cassereau, Patrick Vourc'h, Charlotte Veyrat-Durebex, Hélène Blasco, Selma Kane, Vincent Procaccio, Franck Letournel, Christophe Verny, Guy Lenears, Pascal Reynier, Arnaud Chevrollier
OBJECTIVE: Sporadic amyotrophic lateral sclerosis (sALS) is a fatal neurodegenerative disorder affecting upper and lower motor neurons. In view of the heterogeneous presentation of the disease, one of the current challenges is to identify diagnostic and prognostic markers in order to diagnose sALS at early stage and to stratify patients in trials. In this study, we sought to identify cytological hallmarks of sALS in patient-derived fibroblasts with the aim of finding new clinical-related markers of the disease...
January 31, 2018: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/29382077/vegf-triggers-the-activation-of-cofilin-and-the-arp2-3-complex-within-the-growth-cone
#13
Matthias Schlau, Daniel Terheyden-Keighley, Verena Theis, Hans Georg Mannherz, Carsten Theiss
A crucial neuronal structure for the development and regeneration of neuronal networks is the axonal growth cone. Affected by different guidance cues, it grows in a predetermined direction to reach its final destination. One of those cues is the vascular endothelial growth factor (VEGF), which was identified as a positive effector for growth cone movement. These positive effects are mainly mediated by a reorganization of the actin network. This study shows that VEGF triggers a tight colocalization of cofilin and the Arp2/3 complex to the actin cytoskeleton within chicken dorsal root ganglia (DRG)...
January 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29381886/tubulins-in-c-elegans
#14
Daryl D Hurd
The C.elegans tubulin family is composed of nine α-tubulins, six β-tubulins, and one γ- tubulin. Tubulins are highly conserved, functioning as α-β heterodimers that assemble into microtubules. These cylindrical and ubiquitous components of the cytoskeleton are critical for nearly all cellular and developmental processes. C. elegans has provided a model for the study of microtubules in multiple settings including separation of chromosomes, cellular polarity, and neuronal sensation. Tubulins and microtubules interact with a long list of other cellular proteins that regulate tubulin homeostasis, modify microtubule dynamics, and control incorporation into or disassociation of higher-order cellular structures such as spindles or ciliary axonemes...
January 30, 2018: WormBook: the Online Review of C. Elegans Biology
https://www.readbyqxmd.com/read/29376863/altered-expression-of-circulating-cdc42-in-frontotemporal-lobar-degeneration
#15
Claudia Saraceno, Marcella Catania, Anna Paterlini, Silvia Fostinelli, Miriam Ciani, Roberta Zanardini, Giuliano Binetti, Giuseppe Di Fede, Paola Caroppo, Luisa Benussi, Roberta Ghidoni, Silvia Bolognin
The term frontotemporal lobar degeneration (FTLD) defines a group of heterogeneous conditions histologically characterized by neuronal degeneration, inclusions of various proteins, and synaptic loss. However, the molecular mechanisms contributing to these alterations are still unknown. As the Rho-GTPase family member Cell division cycle 42 (Cdc42) plays a key role in the regulation of actin cytoskeleton dynamics and spine formation, we investigated whether Cdc42 protein levels were altered in the disease. Cdc42 was increased in the frontal cortex of FTLD patients compared to age-matched controls, but also in Alzheimer's disease (AD) patients included in the data-set...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29363583/ephexin1-is-required-for-eph-mediated-limb-trajectory-of-spinal-motor-axons
#16
Chih-Ju Chang, Ming-Yuan Chang, Szu-Yi Chou, Chi-Chen Huang, Jian-Ying Chuang, Tsung-I Hsu, Hsing-Fang Chang, Yi-Hsin Wu, Chung-Che Wu, Daniel Morales, Artur Kania, Tzu-Jen Kao
The precise assembly of a functional nervous system relies on the guided migration of axonal growth cones, which is made possible by signals transmitted to the cytoskeleton by cell surface-expressed guidance receptors. We investigated the function of ephexin1, a Rho guanine nucleotide exchange factor, as an essential growth cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situ mRNA detection, we first show that ephexin1 is expressed in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb...
January 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29358156/the-effects-of-calcineurin-inhibitor-fk506-on-actin-cytoskeleton-neuronal-survival-and-glial-reactions-after-pilocarpine-induced-status-epilepticus-in-mice
#17
Tian-Qing Xiong, Ling-Meng Chen, Bai-Hong Tan, Chun-Yan Guo, Yong-Nan Li, Yan-Feng Zhang, Shu-Lei Li, Hui Zhao, Yan-Chao Li
After status epilepticus (SE), actin cytoskeleton (F-actin) becomes progressively deconstructed in the hippocampus, which is consistent with the delayed pyramidal cell death in both time course and spatial distribution. A variety of experiments show that calcineurin inhibitors such as FK506 are able to inhibit the SE-induced actin depolymerization. However, it is still unclear what changes happen to the F-actin in the epileptic brain after FK506 treatment. A pilocarpine model of SE in mice was used to examine the effects of FK506 on the F-actin in the hippocampal neurons...
January 10, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29340040/identifying-the-dynamics-of-actin-and-tubulin-polymerization-in-ipscs-and-in-ipsc-derived-neurons
#18
Valentina Magliocca, Stefania Petrini, Tiziana Franchin, Rossella Borghi, Alessia Niceforo, Zeinab Abbaszadeh, Enrico Bertini, Claudia Compagnucci
The development of the nervous system requires cytoskeleton-mediated processes coordinating self-renewal, migration, and differentiation of neurons. It is not surprising that many neurodevelopmental problems and neurodegenerative disorders are caused by deficiencies in cytoskeleton-related genes. For this reason, we focus on the cytoskeletal dynamics in proliferating iPSCs and in iPSC-derived neurons to better characterize the underpinnings of cytoskeletal organization looking at actin and tubulin repolymerization studies using the cell permeable probes SiR-Actin and SiR-Tubulin...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338612/gene-profiling-of-nucleus-basalis-tau-containing-neurons-in-chronic-traumatic-encephalopathy-a-chronic-effects-of-neurotrauma-consortium-study
#19
Elliott Jay Mufson, Bin He, Stephen D Ginsberg, Benjamin A Carper, Gayle S Bieler, Fiona C Crawford, Victor E Alverez, Bernard R Huber, Thor D Stein, Ann C McKee, Sylvia E Perez
Military personnel and athletes exposed to traumatic brain injury may develop chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the main constituent of neurofibrillary tangles (NFTs). Recently, we found that cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert (nbM), which provide the major cholinergic innervation to the cortex, display an increasing number of NFTs across the pathological stages of CTE...
January 16, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29330095/crosstalk-between-rac1-mediated-actin-regulation-and-ros-production
#20
REVIEW
Alejandro Acevedo, Christian González-Billault
The small RhoGTPase Rac1 is implicated in a variety of events related to actin cytoskeleton rearrangement. Remarkably, another event that is completely different from those related to actin regulation has the same relevance; the Rac1-mediated production of reactive oxygen species (ROS) through NADPH oxidases (NOX). Each outcome involves different Rac1 downstream effectors; on one hand, events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins and PAKs that ultimately promote actin branching and turnover, on the other, NOX-derived ROS production demands active Rac1 to be bound to a cytosolic activator of NOX...
January 9, 2018: Free Radical Biology & Medicine
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