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https://www.readbyqxmd.com/read/28699521/astrocyte-an-innovative-approach-for-alzheimer-s-disease-therapy
#1
Maria Rosanna Bronzuoli, Roberta Facchinetti, Luca Steardo, Caterina Scuderi
Alzheimer's disease is a devastating neurological illness with a heavy economic impact. Further comorbidity in combination with the social impact of this disorder increases the urgency of a clearer comprehension of its etiopathogenesis, allowing the execution of novel therapeutic strategies. Despite astrocytes have been widely described as active participant in the regulation of cerebral circuits, available data are still poor. Even less information is available about their precise role in the pathogenesis of illness...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28686708/drosophila-lines-with-mutant-and-wild-type-human-tdp-43-replacing-the-endogenous-gene-reveals-phosphorylation-and-ubiquitination-in-mutant-lines-in-the-absence-of-viability-or-lifespan-defects
#2
Jer-Cherng Chang, David B Morton
Mutations in TDP-43 are associated with proteinaceous inclusions in neurons and are believed to be causative in neurodegenerative diseases such as frontotemporal dementia or amyotrophic lateral sclerosis. Here we describe a Drosophila system where we have engineered the genome to replace the endogenous TDP-43 orthologue with wild type or mutant human TDP-43(hTDP-43). In contrast to other models, these flies express both mutant and wild type hTDP-43 at similar levels to those of the endogenous gene and importantly, no age-related TDP-43 accumulation observed among all the transgenic fly lines...
2017: PloS One
https://www.readbyqxmd.com/read/28671695/engineered-aavs-for-efficient-noninvasive-gene-delivery-to-the-central-and-peripheral-nervous-systems
#3
Ken Y Chan, Min J Jang, Bryan B Yoo, Alon Greenbaum, Namita Ravi, Wei-Li Wu, Luis Sánchez-Guardado, Carlos Lois, Sarkis K Mazmanian, Benjamin E Deverman, Viviana Gradinaru
Adeno-associated viruses (AAVs) are commonly used for in vivo gene transfer. Nevertheless, AAVs that provide efficient transduction across specific organs or cell populations are needed. Here, we describe AAV-PHP.eB and AAV-PHP.S, capsids that efficiently transduce the central and peripheral nervous systems, respectively. In the adult mouse, intravenous administration of 1 × 10(11) vector genomes (vg) of AAV-PHP.eB transduced 69% of cortical and 55% of striatal neurons, while 1 × 10(12) vg of AAV-PHP.S transduced 82% of dorsal root ganglion neurons, as well as cardiac and enteric neurons...
June 26, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28671648/acute-in-vivo-electrophysiological-recordings-of-local-field-potentials-and-multi-unit-activity-from-the-hyperdirect-pathway-in-anesthetized-rats
#4
Jens K Haumesser, Johanna Kühn, Christopher Güttler, Dieu-Huong Nguyen, Maximilian H Beck, Andrea A Kühn, Christoph van Riesen
Converging evidence shows that many neuropsychiatric diseases should be understood as disorders of large-scale neuronal networks. To better understand the pathophysiological basis of these diseases, it is necessary to precisely characterize in which way the processing of information is disturbed between the different neuronal parts of the circuit. Using extracellular in vivo electrophysiological recordings, it is possible to accurately delineate neuronal activity within a neuronal network. The application of this method has several advantages over alternative techniques, e...
June 22, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28667479/combining-human-and-rodent-genetics-to-identify-new-analgesics
#5
REVIEW
Alban Latremoliere, Michael Costigan
Most attempts at rational development of new analgesics have failed, in part because chronic pain involves multiple processes that remain poorly understood. To improve translational success, one strategy is to select novel targets for which there is proof of clinical relevance, either genetically through heritable traits, or pharmacologically. Such an approach by definition yields targets with high clinical validity. The biology of these targets can be elucidated in animal models before returning to the patients with a refined therapeutic...
July 1, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28658526/reverse-pharmacogenomics-carbamazepine-normalizes-activation-and-attenuates-thermal-induced-hyperexcitability-of-sensory-neurons-due-to-nav1-7-mutation-i234t
#6
Yang Yang, Talia Adi, Philip Effraim, Lubin Chen, Sulayman D Dib-Hajj, Stephen G Waxman
BACKGROUND AND PURPOSE: Pharmacotherapy for pain currently involves trial-and-error. A previous study on inherited erythromelalgia (a genetic model of neuropathic pain due to mutations in voltage-gated sodium channel Nav1.7) used genomics, structural modeling, biophysical and pharmacological analyses to guide pharmacotherapy, and showed that carbamazepine normalizes voltage-dependence of activation of the Nav1.7-S241T mutant channel, reducing pain in patients carrying this mutation. However, whether this approach is applicable to other Nav mutations is still unknown...
June 28, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28650461/a-light-and-calcium-gated-transcription-factor-for-imaging-and-manipulating-activated-neurons
#7
Wenjing Wang, Craig P Wildes, Tanyaporn Pattarabanjird, Mateo I Sanchez, Gordon F Glober, Gillian A Matthews, Kay M Tye, Alice Y Ting
Activity remodels neurons, altering their molecular, structural, and electrical characteristics. To enable the selective characterization and manipulation of these neurons, we present FLARE, an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically encoded tools only in the subset of neurons that experienced activity during a user-defined time window. FLARE senses the coincidence of elevated cytosolic calcium and externally applied blue light, which together produce translocation of a membrane-anchored transcription factor to the nucleus to drive expression of any transgene...
June 26, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28613457/live-cell-imaging-of-cell-signaling-using-genetically-encoded-fluorescent-reporters
#8
REVIEW
Qiang Ni, Sohum Mehta, Jin Zhang
Synergistic advances in fluorescent protein (FP) engineering and live-cell imaging techniques in recent years have fueled the concurrent development and application of genetically encoded fluorescent reporters that are tailored for tracking signaling dynamics in living systems over multiple length and time scales. These biosensors are uniquely suited for this challenging task, owing to their specificity, sensitivity, and versatility, as well as to the non-invasive and non-destructive nature of fluorescence and the power of genetic encoding...
June 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28613391/evaluation-of-five-diffeomorphic-image-registration-algorithms-for-mouse-brain-magnetic-resonance-microscopy
#9
Zhenrong Fu, Lan Lin, Miao Tian, Jingxuan Wang, Baiwen Zhang, Pingping Chu, Shaowu Li, Muhammad Mohsin Pathan, Yulin Deng, Shuicai Wu
The development of genetically engineered mouse models for neuronal diseases and behavioural disorders have generated a growing need for small animal imaging. High-resolution magnetic resonance microscopy (MRM) provides powerful capabilities for noninvasive studies of mouse brains, while avoiding some limits associated with the histological procedures. Quantitative comparison of structural images is a critical step in brain imaging analysis, which highly relies on the performance of image registration techniques...
June 14, 2017: Journal of Microscopy
https://www.readbyqxmd.com/read/28605376/anatomically-inspired-three-dimensional-micro-tissue-engineered-neural-networks-for-nervous-system-reconstruction-modulation-and-modeling
#10
Laura A Struzyna, Dayo O Adewole, Wisberty J Gordián-Vélez, Michael R Grovola, Justin C Burrell, Kritika S Katiyar, Dmitriy Petrov, James P Harris, D Kacy Cullen
Functional recovery rarely occurs following injury or disease-induced degeneration within the central nervous system (CNS) due to the inhibitory environment and the limited capacity for neurogenesis. We are developing a strategy to simultaneously address neuronal and axonal pathway loss within the damaged CNS. This manuscript presents the fabrication protocol for micro-tissue engineered neural networks (micro-TENNs), implantable constructs consisting of neurons and aligned axonal tracts spanning the extracellular matrix (ECM) lumen of a preformed hydrogel cylinder hundreds of microns in diameter that may extend centimeters in length...
May 31, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28598857/sdf-1-overexpression-by-mesenchymal-stem-cells-enhances-gap-43-positive-axonal-growth-following-spinal-cord-injury
#11
Andrew Nathaniel Stewart, Jessica Jane Matyas, Ryan Matthew Welchko, Alison Delanie Goldsmith, Sarah Elizabeth Zeiler, Ute Hochgeschwender, Ming Lu, Zhenhong Nan, Julien Rossignol, Gary Leo Dunbar
PURPOSE: Utilizing genetic overexpression of trophic molecules in cell populations has been a promising strategy to develop cell replacement therapies for spinal cord injury (SCI). Over-expressing the chemokine, stromal derived factor-1 (SDF-1α), which has chemotactic effects on many cells of the nervous system, offers a promising strategy to promote axonal regrowth following SCI. The purpose of this study was to explore the effects of human SDF-1α, when overexpressed by mesenchymal stem cells (MSCs), on axonal growth and motor behavior in a contusive rat model of SCI...
June 6, 2017: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/28585386/understanding-neurodevelopmental-disorders-using-human-pluripotent-stem-cell-derived-neurons
#12
Claudia Tamburini, Meng Li
Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient-specific cells, which in principle can be differentiated into all disease-relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs-based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed...
July 2017: Brain Pathology
https://www.readbyqxmd.com/read/28580186/mash1-dependent-notch-signaling-pathway-regulates-gabaergic-neuron-like-differentiation-from-bone-marrow-derived-mesenchymal-stem-cells
#13
Qianfa Long, Qiang Luo, Kai Wang, Adrian Bates, Ashok K Shetty
GABAergic neuronal cell grafting has promise for treating a multitude of neurological disorders including epilepsy, age-related memory dysfunction, Alzheimer's disease and schizophrenia. However, identification of an unlimited source of GABAergic cells is critical for advancing such therapies. Our previous study implied that reprogramming of bone marrow-derived mesenchymal stem cells (BMSCs) through overexpression of the Achaete-scute homolog 1 (Ascl1, also called Mash1) could generate GABAergic neuron-like cells...
May 2017: Aging and Disease
https://www.readbyqxmd.com/read/28580010/molecular-and-genetic-insights-into-an-infantile-epileptic-encephalopathy-cdkl5-disorder
#14
Ailing Zhou, Song Han, Zhaolan Joe Zhou
BACKGROUND: The discovery that mutations in cyclin-dependent kinase-like 5 (CDKL5) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. METHODS: A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years...
February 2017: Frontiers in Biology
https://www.readbyqxmd.com/read/28534738/optocontrol-of-glutamate-receptor-activity-by-single-side-chain-photoisomerization
#15
Viktoria Klippenstein, Christian Hoppmann, Shixin Ye, Lei Wang, Pierre Paoletti
Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience. Commonly used tethered photoswitchable ligands, however, require solvent-accessible protein labeling, face structural constrains, and are bulky. Here, we designed a set of optocontrollable NMDA receptors by directly incorporating single photoswitchable amino acids (PSAAs) providing genetic encodability, reversibility, and site tolerance. We identified several positions within the multi-domain receptor endowing robust photomodulation...
May 23, 2017: ELife
https://www.readbyqxmd.com/read/28514167/quantum-dot-peptide-fullerene-bioconjugates-for-visualization-of-in-vitro-and-in-vivo-cellular-membrane-potential
#16
Okhil K Nag, Michael H Stewart, Jeffrey R Deschamps, Kimihiro Susumu, Eunkeu Oh, Vassiliy Tsytsarev, Qinggong Tang, Alexander L Efros, Roman Vaxenburg, Bryan J Black, YungChia Chen, Thomas J O'Shaughnessy, Stella H North, Lauren D Field, Philip E Dawson, Joseph J Pancrazio, Igor L Medintz, Yu Chen, Reha S Erzurumlu, Alan L Huston, James B Delehanty
We report the development of a quantum dot (QD)-peptide-fullerene (C60) electron transfer (ET)-based nanobioconjugate for the visualization of membrane potential in living cells. The bioconjugate is composed of (1) a central QD electron donor, (2) a membrane-inserting peptidyl linker, and (3) a C60 electron acceptor. The photoexcited QD donor engages in ET with the C60 acceptor, resulting in quenching of QD photoluminescence (PL) that tracks positively with the number of C60 moieties arrayed around the QD. The nature of the QD-capping ligand also modulates the quenching efficiency; a neutral ligand coating facilitates greater QD quenching than a negatively charged carboxylated ligand...
June 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28500952/isolation-and-characterization-of-lymphoid-enhancer-factor-1-positive-deciduous-dental-pulp-stem-like-cells-after-transfection-with-a-piggybac-vector-containing-lef1-promoter-driven-selection-markers
#17
Tomoya Murakami, Issei Saitoh, Masahiro Sato, Emi Inada, Miki Soda, Masataka Oda, Hisanori Domon, Yoko Iwase, Tadashi Sawami, Kazunari Matsueda, Yutaka Terao, Hayato Ohshima, Hirofumi Noguchi, Haruaki Hayasaki
OBJECTIVE: Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nuclear protein that is expressed in pre-B and T cells. LEF1 is also an important member of the Wnt/β-catenin signaling pathway that plays important roles in the self-renewal and differentiation of embryonic stem cells. We speculated that LEF1 might function in the stem cells from human exfoliated deciduous teeth (SHED). In this study, we attempted to isolate such LEF1-positive cells from human deciduous dental pulp cells (HDDPCs) by genetic engineering technology, using the human LEF1 promoter...
May 7, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28494742/potential-gene-therapy-towards-treating-neurodegenerative-diseases-employing-polymeric-nanosystems
#18
Prachi Bangde, Sonal Atale, Anomitra Dey, Ashish Pandit, Prajakta Dandekar, Ratnesh Jain
Recent integrated approaches involving nanotechnology and gene therapy have accelerated development of efficient drug delivery to the central nervous system (CNS). Neurodegenerative disorders are closely associated with genetic inheritance and mutation. Nanotechnology has allowed effective engineering of various such polymeric structures. Moreover, availability of a wide array of polymeric materials has enabled fabrication of biocompatible and biodegradable delivery vehicles. Our review focuses on the ideal features and properties of polymeric nanoparticles that have enabled successful gene therapy for neurodegenerative disorders, as well as the challenges that are posing difficulties in their practical application...
May 10, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28490756/expressing-acetylcholine-receptors-after-innervation-suppresses-spontaneous-vesicle-release-and-causes-muscle-fatigue
#19
Meghan Mott, Victor M Luna, Jee-Young Park, Gerald B Downes, Kimberly Epley, Fumihito Ono
The formation and function of synapses are tightly orchestrated by the precise timing of expression of specific molecules during development. In this study, we determined how manipulating the timing of expression of postsynaptic acetylcholine receptors (AChRs) impacts presynaptic release by establishing a genetically engineered zebrafish line in which we can freely control the timing of AChR expression in an AChR-less fish background. With the delayed induction of AChR expression after an extensive period of AChR-less development, paralyzed fish displayed a remarkable level of recovery, exhibiting a robust escape response following developmental delay...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28482609/combining-nt3-overexpressing-mscs-and-plga-microcarriers-for-brain-tissue-engineering-a-potential-tool-for-treatment-of-parkinson-s-disease
#20
Hanieh Moradian, Hamid Keshvari, Hamidreza Fasehee, Rassoul Dinarvand, Shahab Faghihi
Parkinson's disease (PD) is a progressive neurodegenerative disorder that characterized by destruction of substantia nigrostriatal pathway due to the loss of dopaminergic (DA) neurons. Regardless of substantial efforts for treatment of PD in recent years, an effective therapeutic strategy is still missing. In a multidisciplinary approach, bone marrow derived mesenchymal stem cells (BMSCs) are genetically engineered to overexpress neurotrophin-3 (nt-3 gene) that protect central nervous system tissues and stimulates neuronal-like differentiation of BMSCs...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
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