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https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#1
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28634550/sortilin-related-receptor-expression-in-human-neural-stem-cells-derived-from-alzheimer-s-disease-patients-carrying-the-apoe-epsilon-4-allele
#2
Alen Zollo, Zoe Allen, Helle F Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten J Maier, Carmela Matrone
Alzheimer's disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28634261/autophagy-gene-fip200-in-neural-progenitors-non-cell-autonomously-controls-differentiation-by-regulating-microglia
#3
Chenran Wang, Syn Yeo, Michael A Haas, Jun-Lin Guan
Recent studies have shown important roles for autophagy genes in the regulation of different tissue stem cells, including neural stem/progenitor cells (NSCs). However, little is known about whether autophagy can regulate NSCs through cell-extrinsic mechanisms. Here, we show that deletion of an essential autophagy gene, FIP200, in NSCs increased expression of Ccl5 and Cxcl10 in a p53-independent manner, mediating increased infiltration of microglia into the subventricular zone of both FIP200hGFAP conditional knockout (cKO) and FIP200;p53hGFAP 2cKO mice...
June 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28632448/neuroregeneration-versus-neurodegeneration-toward-a-paradigm-shift-in-alzheimer-s-disease-drug-discovery
#4
Elisa Uliassi, Annachiara Gandini, Rosaria Carmela Perone, Maria Laura Bolognesi
Alzheimer's disease represents an enormous global burden in terms of human suffering and economic cost. To tackle the current lack of effective drugs and the continuous clinical trial failures might require a shift from the prevailing paradigm targeting pathogenesis to the one targeting neural stem cells (NSCs) regeneration. In this context, small molecules have come to the forefront for their potential to manipulate NSCs, provide therapeutic tools and unveil NSCs biology. Classically, these molecules have been generated either by target-based or phenotypic approaches...
June 20, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28631858/sensory-response-in-host-and-engrafted-astrocytes-of-adult-brain-in-vivo
#5
REVIEW
Kuan Zhang, Xiaowei Chen
Rapid advances in Ca(2+) imaging techniques enable us to simultaneously monitor the activities of hundreds of astrocytes in the intact brain, thus providing a powerful tool for understanding the functions of both host and engrafted astrocytes in sensory processing in vivo. These techniques include both improved Ca(2+) indicators and advanced optical recording methods. Astrocytes in multiple cortical and sub-cortical areas are able to respond to the corresponding sensory modalities. These sensory stimuli produce astrocytic Ca(2+) responses through different cellular mechanisms...
June 20, 2017: Glia
https://www.readbyqxmd.com/read/28630630/roles-of-mesenchymal-stem-cells-in-spinal-cord-injury
#6
REVIEW
Jing Qu, Huanxiang Zhang
Spinal cord injury (SCI) represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS) impairments, which is still beyond functional regeneration. Transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28629798/proteomic-analysis-of-mesenchymal-to-schwann-cell-transdifferentiation
#7
Anup D Sharma, Jayme Wiederin, Metin Uz, Pawel Ciborowski, Surya K Mallapragada, Howard E Gendelman, Donald S Sakaguchi
While transplantation of Schwann cells facilitates axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of autologous bone-marrow derived mesenchymal stem cells (MSCs). As MSCs can transdifferentiate to Schwann cell-phenotypes and accelerate nerve regeneration we undertook proteomic evaluation of the cells to uncover the protein contents that affects Schwann cell formulation...
June 16, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28627669/recovery-of-spinal-cord-injury-following-electroacupuncture-in-rats-through-enhancement-of-wnt-%C3%AE-catenin-signaling
#8
Junfeng Zhang, Shisheng Li, Yaochi Wu
Electroacupuncture (EA) has been demonstrated to promote the functional recovery of neurons following spinal cord injury (SCI); however, the mechanisms underlying its effects have yet to be elucidated. The Wnt/β-catenin signaling pathway has been implicated in the regulation of the balance between growth, proliferation and differentiation of neural precursor cells. The present study aimed to investigate the effects of EA therapy on Wnt/β‑catenin‑regulated gene expression and neuronal recovery in rats with SCI...
June 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627367/nrf2-pathway-activation-upon-rotenone-treatment-in-human-ipsc-derived-neural-stem-cells-undergoing-differentiation-towards-neurons-and-astrocytes
#9
Francesca Pistollato, David Canovas-Jorda, Dimitra Zagoura, Anna Bal-Price
Activation of Nrf2/ARE signaling pathway occurs ubiquitously in most cell types upon induction of oxidative stress. Rotenone, an inhibitor of mitochondrial complex I, can be used to trigger oxidative stress, stimulate the activation of Nrf2 pathway in neuronal and astrocytic cells and assess neurotoxicity. We have previously demonstrated that an acute treatment with rotenone can induce Nrf2 activation, which leads to astrocyte activation and dopaminergic (DA) neuronal cell death in a mixed neuronal/astrocytic cell model derived from human induced pluripotent stem cells (hiPSCs)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28627366/pqbp1-an-intrinsically-disordered-denatured-protein-at-the-crossroad-of-intellectual-disability-and-neurodegenerative-diseases
#10
REVIEW
Hitoshi Okazawa
PQBP1 (polyglutamine binding protein-1) is the earliest identified molecule among the group of disease-related intrinsically disordered/denatured proteins. PQBP1 interacts with splicing-related factors via the disordered/denatured domain and regulates post-transcriptional gene expression. The mutations cause intellectual disability due to decreased dendritic spines and abnormal expression of synapse molecules in neurons, and microcephaly due to elongated cell cycle time and abnormal expression of cell cycle proteins in neural stem progenitor cells...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28627365/mitochondria-metabolic-reprogramming-in-the-formation-of-neurons-from-peripheral-cells-cause-or-consequence-and-the-implications-to-their-utility
#11
REVIEW
Gary E Gibson, Ankita Thakkar
The induction of pluripotent stem cells (iPSC) from differentiated cells such as fibroblasts and their subsequent conversion to neural progenitor cells (NPC) and finally to neurons is intriguing scientifically, and its potential to medicine nearly infinite, but unrealized. A better understanding of the changes at each step of the transformation will enable investigators to use them better to model neurological disease. Each step of conversion from a differentiated cell to an iPSC to a NPC to neurons requires large changes in glycolysis including aerobic glycolysis, the pentose shunt, the tricarboxylic acid cycle, the electron transport chain and in the production of reactive oxygen species (ROS)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28626748/the-multiple-roles-of-fgf-signaling-in-the-developing-spinal-cord
#12
REVIEW
Ruth Diez Del Corral, Aixa V Morales
During vertebrate embryonic development, the spinal cord is formed by the neural derivatives of a neuromesodermal population that is specified at early stages of development and which develops in concert with the caudal regression of the primitive streak. Several processes related to spinal cord specification and maturation are coupled to this caudal extension including neurogenesis, ventral patterning and neural crest specification and all of them seem to be crucially regulated by Fibroblast Growth Factor (FGF) signaling, which is prominently active in the neuromesodermal region and transiently in its derivatives...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28626459/the-immunogenicity-and-immune-tolerance-of-pluripotent-stem-cell-derivatives
#13
REVIEW
Xin Liu, Wenjuan Li, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28626389/rac1-guides-porf-2-to-wnt-pathway-to-mediate-neural-stem-cell-proliferation
#14
Xi-Tao Yang, Guo-Hui Huang, Hong-Jiang Li, Zhao-Liang Sun, Nan-Jie Xu, Dong-Fu Feng
The molecular and cellular mechanisms underlying the anti-proliferative effects of preoptic regulator factor 2 (Porf-2) on neural stem cells (NSCs) remain largely unknown. Here, we found that Porf-2 inhibits the activity of ras-related C3 botulinum toxin substrate 1 (Rac1) protein in hippocampus-derived rat NSCs. Reduced Rac1 activity impaired the nuclear translocation of β-catenin, ultimately causing a repression of NSCs proliferation. Porf-2 knockdown enhanced NSCs proliferation but not in the presence of small molecule inhibitors of Rac1 or Wnt...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28625813/neurogenesis-in-the-aging-brain
#15
REVIEW
Deana M Apple, Rene Solano-Fonseca, Erzsebet Kokovay
Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair...
June 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28625535/glial-specific-functions-of-microcephaly-protein-wdr62-and-interaction-with-the-mitotic-kinase-aurka-are-essential-for-drosophila-brain-growth
#16
Nicholas R Lim, Belal Shohayeb, Olga Zaytseva, Naomi Mitchell, S Sean Millard, Dominic C H Ng, Leonie M Quinn
The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume...
June 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28624056/evaluating-the-efficacy-of-different-types-of-stem-cells-in-preserving-gut-barrier-function-in-necrotizing-enterocolitis
#17
Christopher J McCulloh, Jacob K Olson, Yijie Wang, Jennifer Vu, Sarah Gartner, Gail E Besner
BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. Increased intestinal permeability is central to NEC development. We have shown that stem cells (SCs) can reduce the incidence and severity of NEC. Our current goal was to investigate the efficacy of four different types of SC in preservation of gut barrier function during NEC. MATERIALS AND METHODS: We compared (1) amniotic fluid-derived mesenchymal SC, (2) bone marrow-derived mesenchymal SC, (3) amniotic fluid-derived neural SC, and (4) enteric neural SC...
June 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28623786/proteolytic-processed-form-of-cxcl12-abolishes-migration-and-induces-apoptosis-in-neural-stem-cells-in-vitro
#18
Taís Adelita, Roberta Sessa Stilhano, Sang Won Han, Giselle Zenker Justo, Marimelia Porcionatto
The subventricular zone (SVZ) of the adult mammalian brain hosts full potential neural stem cells (NSCs). NSCs are able to respond to extracellular signals in the brain, amplifying the pool of progenitor cells and giving rise to neuroblasts that show ability to migrate towards an injury site. These signals can come from vascular system, cerebrospinal fluid, glial cells, or projections of neurons in adjoining regions. CXCL12, a chemokine secreted after brain injury, reaches the SVZ in a gradient manner and drives neuroblasts towards the lesion area...
June 4, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28623617/decrease-in-adult-neurogenesis-and-neuroinflammation-are-involved-in-spatial-memory-impairment-in-the-streptozotocin-induced-model-of-sporadic-alzheimer-s-disease-in-rats
#19
Taysa Bervian Bassani, Jéssica M Bonato, Meira M F Machado, Valentín Cóppola-Segovia, Eric L R Moura, Silvio M Zanata, Rúbia M M W Oliveira, Maria A B F Vital
Early impairments in cerebral glucose metabolism and insulin signaling pathways may participate in the pathogenesis of the sporadic form of Alzheimer's disease (sAD). Intracerebroventricular (ICV) injections of low doses of streptozotocin (STZ) are used to mimic sAD and study these alterations in rodents. Streptozotocin causes impairments in insulin signaling and has been reported to trigger several alterations in the brain, such as oxidative stress, neuroinflammation, and dysfunctions in adult neurogenesis, which may be involved in cognitive decline and are features of human AD...
June 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28623616/cyclosporine-a-mediated-il-6-expression-promotes-neural-induction-in-pluripotent-stem-cells
#20
Ashwathnarayan Ashwini, Sushma S Naganur, Bhaskar Smitha, Preethi Sheshadri, Jyothi Prasanna, Anujith Kumar
Differentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis. To extend the information to in vitro neurogenesis, we examined the effect of CsA on neural differentiation of PSCs...
June 16, 2017: Molecular Neurobiology
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