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https://www.readbyqxmd.com/read/28941357/microrna-in-alzheimer-s-disease-revisited-implications-for-major-neuropathological-mechanisms
#1
Reihaneh Dehghani, Farzaneh Rahmani, Nima Rezaei
Pathology of Alzheimer's disease (AD) goes far beyond neurotoxicity resulting from extracellular deposition of amyloid β (Aβ) plaques. Aberrant cleavage of amyloid precursor protein and accumulation of Aβ in the form of the plaque or neurofibrillary tangles are the known primary culprits of AD pathogenesis and target for various regulatory mechanisms. Hyper-phosphorylation of tau, a major component of neurofibrillary tangles, precipitates its aggregation and prevents its clearance. Lipid particles, apolipoproteins and lipoprotein receptors can act in favor or against Aβ and tau accumulation by altering neural membrane characteristics or dynamics of transport across the blood-brain barrier...
September 23, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28938008/vca-nanobodies-target-n-wasp-to-reduce-invadopodium-formation-and-functioning
#2
Tim Hebbrecht, Isabel Van Audenhove, Olivier Zwaenepoel, Adriaan Verhelle, Jan Gettemans
Invasive cancer cells develop small actin-based protrusions called invadopodia, which perform a primordial role in metastasis and extracellular matrix remodelling. Neural Wiskott-Aldrich syndrome protein (N-WASp) is a scaffold protein which can directly bind to actin monomers and Arp2/3 and is a crucial player in the formation of an invadopodium precursor. Expression modulation has pointed to an important role for N-WASp in invadopodium formation but the role of its C-terminal VCA domain in this process remains unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28928809/nedd4-promotes-cell-growth-and-migration-via-pten-pi3k-akt-signaling-in-hepatocellular-carcinoma
#3
Zhi-Jun Huang, Jun-Jun Zhu, Xiao-Yu Yang, Ewelina Biskup
The novel E3 ubiquitin-protein ligase neural precursor cell-expressed developmentally downregulated protein 4 (NEDD4) has been implicated as a crucial factor promoting the tumorigenesis of several types of cancer. The present study investigated the oncogenic role of NEDD4 in hepatocellular carcinoma (HCC) by targeted small interfering RNA silencing of the tumor suppressor phosphatase and tensin homolog (PTEN). Using normal hepatocyte and HCC cell lines, the influence of NEDD4 depletion on proliferation and migration as well as on the PTEN/phosphatidylinositol-3-kinase/protein kinase B signaling pathway was assessed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928414/disruption-to-schizophrenia-associated-gene-fez1-in-the-hippocampus-of-hdac11-knockout-mice
#4
Dale T Bryant, Christian Landles, Aikaterini S Papadopoulou, Agnesska C Benjamin, Joshua K Duckworth, Thomas Rosahl, Caroline L Benn, Gillian P Bates
Histone Deacetylase 11 (HDAC11) is highly expressed in the central nervous system where it has been reported to have roles in neural differentiation. In contrast with previous studies showing nuclear and cytoplasmic localisation, we observed synaptic enrichment of HDAC11. Knockout mouse models for HDACs 1-9 have been important for guiding the development of isoform specific HDAC inhibitors as effective therapeutics. Given the close relationship between HDAC11 and neural cells in vitro, we examined neural tissue in a previously uncharacterised Hdac11 knockout mouse (Hdac11 (KO/KO))...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927893/msx1-induced-neural-crest-like-reprogramming-promotes-melanoma-progression
#5
Markus V Heppt, Joshua X Wang, Denitsa M Hristova, Zhi Wei, Ling Li, Brianna Evans, Marilda Beqiri, Samir Zaman, Jie Zhang, Martin Irmler, Carola Berking, Robert Besch, Johannes Beckers, Frank J Rauscher, Rick A Sturm, David E Fisher, Meenhard Herlyn, Mizuho Fukunaga-Kalabis
Melanoma cells share many biological properties with neural crest stem cells. Here we show that the homeodomain transcription factor Msh homeobox 1 (MSX1), which is significantly correlated with melanoma disease progression, reprograms melanocytes and melanoma cells towards a neural crest precursor-like state. MSX1-reprogrammed normal human melanocytes express the neural crest marker p75 and become multipotent. MSX1 induces a phenotypic switch in melanoma, which is characterized by an oncogenic transition from an E-cadherin-high non-migratory state towards a ZEB1-high invasive state...
September 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28925069/myelin-plasticity-neural-activity-and-traumatic-neural-injury
#6
REVIEW
Bethany R Kondiles, Philip J Horner
The possibility that adult organisms exhibit myelin plasticity has recently become a topic of great interest. Many researchers are exploring the role of myelin growth and adaptation in daily functions such as memory and motor learning. Here we consider evidence for three different potential categories of myelin plasticity: the myelination of previously bare axons, remodeling of existing sheaths, and the removal of a sheath with replacement by a new internode. We also review evidence that points to the importance of neural activity as a mechanism by which oligodendrocyte precursor cells (OPCs) are cued to differentiate into myelinating oligodendrocytes, which may potentially be an important component of myelin plasticity...
September 19, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28923480/impact-of-morphine-on-the-expression-of-insulin-receptor-and-protein-levels-of-insulin-igfs-in-rat-neural-stem-cells
#7
Sadegh Salarinasab, AliReza Nourazarian, Masoud Nikanfar, Nima Abdyazdani, Masoumeh Kazemi, Navid Feizy, Reza Rahbarghazi
Alzheimer's disease is correlated with neuronal degeneration and loss of neuronal precursors in different parts of the brain. It has been found disturbance in the homeostasis neural stem cells (NSCs) can cause neurodegeneration. Morphine, an analgesic agent, can disrupt the dynamic and normal state of NSCs. However, more investigations are required to clearly address underlying mechanisms. The current experiment aimed to investigate the effects of morphine on the cell distribution of insulin factor and receptor and insulin-like growth factors (IGF1, IGF2) in NSCs...
September 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28919436/the-notch-pathway-regulates-the-second-mitotic-wave-cell-cycle-independently-of-bhlh-proteins
#8
Abhishek Bhattacharya, Ke Li, Manon Quiquand, Gerard Rimesso, Nicholas E Baker
Notch regulates both neurogenesis and cell cycle activity to coordinate precursor cell generation in the differentiating Drosophila eye. Mosaic analysis with mitotic clones mutant for Notch components was used to identify the pathway of Notch signaling that regulates the cell cycle in the Second Mitotic Wave. Although S phase entry depends on Notch signaling and on the transcription factor Su(H), the transcriptional co-activator Mam and the bHLH repressor genes of the E(spl)-Complex were not essential, although these are Su(H) coactivators and targets during the regulation of neurogenesis...
September 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28913662/effects-of-short-term-exposure-to-sevoflurane-on-the-survival-proliferation-apoptosis-and-differentiation-of-neural-precursor-cells-derived-from-human-embryonic-stem-cells
#9
Jin-Woo Park, Mi-Sun Lim, So Yeon Ji, Myung Soo Cho, Seong-Joo Park, Sung-Hee Han, Jin-Hee Kim
PURPOSE: Data from animal experiments suggest that exposure to general anesthetics in early life inhibits neurogenesis and causes long-term memory deficit. Considering short operating times and the popularity of sevoflurane in pediatric anesthesia, it is important to verify the effects of short-period exposure to sevoflurane on the developing brain. METHODS: We measured the effects of short-term exposure (2 h) to 3%, 6%, or 8% sevoflurane, the most commonly used anesthetic, on neural precursor cells derived from human embryonic stem cells, SNUhES32...
September 14, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28901192/neuronal-cell-sheets-of-cortical-motor-neuron-phenotype-derived-from-human-ipscs
#10
Noboru Suzuki, Nagisa Arimitsu, Jun Shimizu, Kenji Takai, Chieko Hirotsu, Yuji Ueda, Sueshige Wakisaka, Naruyoshi Fujiwara, Tomoko Suzuki
Transplantation of stem cells that differentiate into more mature neural cells brings about functional improvement in preclinical studies of stroke. Previous transplant approaches in the diseased brain utilized injection of the cells in a cell suspension. In addition, neural stem cells were preferentially used for grafting. However, these cells had no specific relationship to the damaged tissue of stroke and brain injury patients. The injection of cells in a suspension destroyed the cell-cell interactions that are suggested to be important for promoting functional integrity of cortical motor neurons...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28899812/the-starving-brain-overfed-meets-undernourished-in-the-pathology-of-mild-cognitive-impairment-mci-and-alzheimer-s-disease-ad
#11
REVIEW
Kelly J Gibas
Type II Diabetes affects 400 million people worldwide (IDF, 2013). The pathology is paradoxical: internal starvation activated by overfeeding. Hyperinsulinemic impairments of glucose homeostasis are treated with anti-hyperglycemics exacerbating cell starvation, inducing hypoglycemia and raising respiratory quotient. Reductions in hyperglycemia are achieved at the expense of glucose dependency and metabolic inflexibility (Gibas & Gibas, 2017). The brain is not immune from these cycles of starvation. The bioenergetic model characterizes propagation of late-onset, sporadic Alzheimer's disease as loss of molecular fidelity and compromised energy originating in brain networks with highest metabolic demand...
September 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28895456/spatial-and-cellular-expression-patterns-of-erythropoietin-receptor-and-erythropoietin-during-a-42-day-post-lesional-time-course-after-graded-thoracic-spinal-cord-impact-lesions-in-the-rat
#12
Gesa Cohrs, Stephan Goerden, Ralf Lucius, Michael Synowitz, Maximilian Hubertus Mehdorn, Janka Held-Feindt, Friederike Knerlich-Lukoschus
Erythropoietin (Epo) exhibits promising neuroregenerative potential for spinal cord injury (SCI) and might be involved in other long-term sequelae, such as neuropathic pain development. The current studies investigated the time courses and spatial and cellular patterns of Epo and EpoR expression along the spinal axis after graded SCI. Male Long Evans rats received 100-kdyn, 150-kdyn, and 200-kdyn thoracic (T9) contusions from an Infinite Horizon Impactor. Sham controls received laminectomies. Anatomical and quantitative immunohistochemical analyses of the EpoR/Epo expression along the whole spinal axis were performed 7, 15, and 42 DPO after the lesioning...
September 12, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28893649/endothelial-cells-maintain-neural-stem-cells-quiescent-in-their-niche
#13
Patrick O Azevedo, Luiza Lousado, Ana E Paiva, Julia P Andreotti, Gabryella S P Santos, Isadora F G Sena, Pedro H D M Prazeres, Renato Filev, Akiva Mintz, Alexander Birbrair
Niches are specialized microenvironments that regulate stem cells activity. The neural stem cell (NSC) niche defines a zone in which NSCs are retained and produce new cells of the nervous system throughout life. Understanding the signaling mechanisms by which the nichecontrols theNSC fate is crucial for the success of clinical applications. In a recent study, Sato and colleagues, by using state-of-the-art techniques, including sophisticated in vivo lineage-tracing technologies, provide evidence that endothelial amyloid precursor protein (APP) is an important component of the NSC niche...
September 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/28892064/a-mouse-model-for-embryonal-tumors-with-multilayered-rosettes-uncovers-the-therapeutic-potential-of-sonic-hedgehog-inhibitors
#14
Julia E Neumann, Annika K Wefers, Sander Lambo, Edoardo Bianchi, Marie Bockstaller, Mario M Dorostkar, Valerie Meister, Pia Schindler, Andrey Korshunov, Katja von Hoff, Johannes Nowak, Monika Warmuth-Metz, Marlon R Schneider, Ingrid Renner-Müller, Daniel J Merk, Mehdi Shakarami, Tanvi Sharma, Lukas Chavez, Rainer Glass, Jennifer A Chan, M Mark Taketo, Philipp Neumann, Marcel Kool, Ulrich Schüller
Embryonal tumors with multilayered rosettes (ETMRs) have recently been described as a new entity of rare pediatric brain tumors with a fatal outcome. We show here that ETMRs are characterized by a parallel activation of Shh and Wnt signaling. Co-activation of these pathways in mouse neural precursors is sufficient to induce ETMR-like tumors in vivo that resemble their human counterparts on the basis of histology and global gene-expression analyses, and that point to apical radial glia cells as the possible tumor cell of origin...
September 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28884193/neurotrophin-trk-receptors-new-targets-for-cancer-therapy
#15
Jacopo Meldolesi
In the last few years, exciting reports have emerged regarding the role of the two types of neurotrophin receptors, p75(NTR) and Trks, not only in neurons, where they were discovered, but also in non-neural cells and, especially, in numerous cancers, including breast, lung, colon-rectum, pancreas, prostate, glioblastoma, neuroblastoma, myeloma, and lymphoid tumors. Traditionally, p75(NTR), activated by all neurotrophins and their precursors, is an inhibitor. In various cancers, however, activated p75(NTR) induces variable effects, from inhibition to stimulation of cell proliferation, dependent on their direct or coordinate/indirect mechanism(s) of action...
September 8, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28882971/mouse-hemokinin-1-decapeptide-subjected-to-a-brain-specific-post-translational-modification
#16
Georgia Deliconstantinos, Stephen Barton, Mikhail Soloviev, Nigel Page
BACKGROUND/AIM: The tachykinin mouse hemokinin-1, expressed by the mouse Tac4 gene, produces either analgesia or nociception, interacting with the neurokinin 1 receptor. TAC4 precursor processing is not identical to the processing of the TAC1 precursor, for the release of substance P (amidated undecapeptide). The characterization of the mouse hemokinin-1 sequence was required. MATERIALS AND METHODS: We developed anti-tachykinin-specific antibodies for the immunoaffinity purification of tachykinins...
September 2017: In Vivo
https://www.readbyqxmd.com/read/28882412/a-flavonoid-agonist-of-the-trkb-receptor-for-bdnf-improves-hippocampal-neurogenesis-and-hippocampus-dependent-memory-in-the-ts65dn-mouse-model-of-ds
#17
Fiorenza Stagni, Andrea Giacomini, Sandra Guidi, Marco Emili, Beatrice Uguagliati, Maria Elisa Salvalai, Valeria Bortolotto, Mariagrazia Grilli, Roberto Rimondini, Renata Bartesaghi
Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB)...
September 4, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28878619/mirna-enriched-in-human-neuroblast-nuclei-bind-the-maz-transcription-factor-and-their-precursors-contain-the-maz-consensus-motif
#18
Belinda J Goldie, Chantel Fitzsimmons, Judith Weidenhofer, Joshua R Atkins, Dan O Wang, Murray J Cairns
While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterized. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enriched in the nucleus. These molecules were predominantly primate-specific and contained a sequence motif with homology to the consensus MAZ transcription factor binding element. Precursor miRNA containing this motif were shown to have affinity for MAZ protein in nuclear extract...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28878618/the-non-survival-effects-of-glial-cell-line-derived-neurotrophic-factor-on-neural-cells
#19
REVIEW
Daniel Cortés, Oscar A Carballo-Molina, María José Castellanos-Montiel, Iván Velasco
Glial cell line-derived neurotrophic factor (GDNF) was first characterized as a survival-promoting molecule for dopaminergic neurons (DANs). Afterwards, other cells were also discovered to respond to GDNF not only as a survival factor but also as a protein supporting other cellular functions, such as proliferation, differentiation, maturation, neurite outgrowth and other phenomena that have been less studied than survival and are now more extendedly described here in this review article. During development, GDNF favors the commitment of neural precursors towards dopaminergic, motor, enteric and adrenal neurons; in addition, it enhances the axonal growth of some of these neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28874392/zika-virus-has-oncolytic-activity-against-glioblastoma-stem-cells
#20
Zhe Zhu, Matthew J Gorman, Lisa D McKenzie, Jiani N Chai, Christopher G Hubert, Briana C Prager, Estefania Fernandez, Justin M Richner, Rong Zhang, Chao Shan, Eric Tycksen, Xiuxing Wang, Pei-Yong Shi, Michael S Diamond, Jeremy N Rich, Milan G Chheda
Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells...
September 5, 2017: Journal of Experimental Medicine
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