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https://www.readbyqxmd.com/read/29156730/generation-of-patient-specific-human-neural-stem-cells-from-niemann-pick-disease-type-c-patient-derived-fibroblasts
#1
Eun-Ah Sung, Kyung-Rok Yu, Ji-Hee Shin, Yoojin Seo, Hyung-Sik Kim, Myung Guen Koog, Insung Kang, Jae-Jun Kim, Byung-Chul Lee, Tae-Hoon Shin, Jin Young Lee, Seunghee Lee, Tae-Wook Kang, Soon Won Choi, Kyung-Sun Kang
Niemann-Pick disease type C (NPC) is a neurodegenerative and lysosomal lipid storage disorder, characterized by the abnormal accumulation of unesterified cholesterol and glycolipids, which is caused by mutations in the NPC1 genes. Here, we report the generation of human induced neural stem cells from NPC patient-derived fibroblasts (NPC-iNSCs) using only two reprogramming factors SOX2 and HMGA2 without going through the pluripotent state. NPC-iNSCs were stably expandable and differentiated into neurons, astrocytes, and oligodendrocytes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149058/neurotrophic-and-neuroregenerative-effects-of-gh-igf1
#2
Vittorio Emanuele Bianchi, Vittorio Locatelli, Laura Rizzi
INTRODUCTION: Human neurodegenerative diseases increase progressively with age and present a high social and economic burden. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are both growth factors exerting trophic effects on neuronal regeneration in the central nervous system (CNS) and peripheral nervous system (PNS). GH and IGF-1 stimulate protein synthesis in neurons, glia, oligodendrocytes, and Schwann cells, and favor neuronal survival, inhibiting apoptosis. This study aims to evaluate the effect of GH and IGF-1 on neurons, and their possible therapeutic clinical applications on neuron regeneration in human subjects...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29140922/fingolimod-reduces-neuropathic-pain-behaviors-in-a-mouse-model-of-multiple-sclerosis-by-a-sphingosine-1-phosphate-receptor-1-dependent-inhibition-of-central-sensitization-in-the-dorsal-horn
#3
Suzanne Doolen, Tommaso Iannitti, Benjamin C Shaw, Carolyn M Grachen, Renee R Donahue, Bradley K Taylor
Multiple sclerosis (MS) is an autoimmune-inflammatory neurodegenerative disease that is often accompanied by a debilitating neuropathic pain. Disease-modifying agents slow the progression of MS and prevent relapses, yet it remains unclear if they yield analgesia. We explored the analgesic potential of fingolimod (FTY720), an agonist/functional antagonist at the sphingosine-1-phosphate receptor 1 (S1PR1), because it reduces hyperalgesia in models of peripheral inflammatory and neuropathic pain. We used a myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) mouse model of experimental autoimmune encephalomyelitis (EAE), modified to avoid frank paralysis and thus allow for assessment of withdrawal behaviors to somatosensory stimuli...
November 13, 2017: Pain
https://www.readbyqxmd.com/read/29137922/extracellular-vesicles-in-neurodegenerative-diseases
#4
REVIEW
Tommaso Croese, Roberto Furlan
Extracellular vesicles (EVs) are released by all neural cells, including neurons, oligodendrocytes, astrocytes, and microglia. The lack of adequate technology has not halted neuroscientists from investigating EVs as a mean to decipher neurodegenerative disorders, still in search of comprehensible pathogenic mechanisms and efficient treatment. EVs are thought to be one of ways neurodegenerative pathologies spread in the brain, but also one of the ways the brain tries to displace toxic proteins, making their meaning in pathogenesis uncertain...
November 11, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29133394/role-of-estrogen-receptor-beta-in-neural-differentiation-of-mouse-embryonic-stem-cells
#5
Mukesh K Varshney, José Inzunza, Diana Lupu, Vaidheeswaran Ganapathy, Per Antonson, Joëlle Rüegg, Ivan Nalvarte, Jan-Åke Gustafsson
The ability to propagate mature cells and tissue from pluripotent stem cells offers enormous promise for treating many diseases, including neurodegenerative diseases. Before such cells can be used successfully in neurodegenerative diseases without causing unwanted cell growth and migration, genes regulating growth and migration of neural stem cells need to be well characterized. Estrogen receptor beta (ERβ) is essential for migration of neurons and glial cells in the developing mouse brain. To examine whether ERβ influences differentiation of mouse embryonic stem cells (mESC) into neural lineages, we compared control and ERβ knockout (BERKO) mESCs at defined stages of neural development and examined the effects of an ERβ-selective ligand (LY3201) with a combination of global and targeted gene-expression profiling and the expression of key pluripotency markers...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29123152/neural-specific-deletion-of-mitochondrial-p32-c1qbp-leads-to-leukoencephalopathy-due-to-undifferentiated-oligodendrocyte-and-axon-degeneration
#6
Mikako Yagi, Takeshi Uchiumi, Noriaki Sagata, Daiki Setoyama, Rie Amamoto, Yuichi Matsushima, Dongchon Kang
Mitochondrial dysfunction is a critical step in the pathogenesis of many neurodegenerative diseases. The p32/ C1qbp gene functions as an essential RNA and protein chaperone in mitochondrial translation, and is indispensable for embryonic development. However, little is known about the consequences of mitochondrial dysfunction of p32 deletion in the brain development. Here, we found that mice lacking p32 in the central nervous system (p32cKO mice) showed white matter degeneration accompanied by progressive oligodendrocyte loss, axon degeneration and vacuolation in the mid brain and brain stem regions...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120167/understanding-the-inflammatory-tissue-reaction-to-brain-implants-to-improve-neurochemical-sensing-performance
#7
Steven M Wellman, Takashi D Y Kozai
Neurochemical sensing probes are a valuable diagnostic and therapeutic tool that can be used to study neurodegenerative diseases involving deficiencies in neurotransmitter signaling. However, implantation of these biosensors can elicit a harmful tissue response that alters the neurochemical environment within the brain. Transmission of chemical messengers via neurons is impeded by a barrier-forming glial scar that occurs within weeks after insertion followed by progressive neurodegeneration, attenuating signal sensitivity...
November 9, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29115515/serum-microrna-expression-profiling-in-patients-with-multiple-system-atrophy
#8
Kodai Kume, Hisakazu Iwama, Kazushi Deguchi, Kazuyo Ikeda, Tadayuki Takata, Yohei Kokudo, Masaki Kamada, Keiko Fujikawa, Kayo Hirose, Hisashi Masugata, Tetsuo Touge, Tsutomu Masaki
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease that is pathologically characterized by α‑synuclein positive glial cytoplasmic inclusions in oligodendrocytes. The clinical diagnosis of MSA is often challenging as there are no established biomarkers and diagnoses are now based on clinical findings alone. At present, the etiology and pathogenesis of MSA are unclear. It has been reported that dysregulation of microRNA (miRNA/miR) serves an important role in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29114585/the-influence-of-retinoic-acid-on-the-human-oligodendrocyte-precursor-cells-by-rna-sequencing
#9
Sun Young Kim, Eve E Kelland, Ji Hong Kim, Brett T Lund, Xiao Chang, Kai Wang, Leslie P Weiner
Retinoic acid (RA), a metabolite of vitamin A, has been found to influence regeneration in the adult central nervous system (CNS). There may be an effect of RA in the recovery/repair in multiple sclerosis (MS), an autoimmune and neurodegenerative disease of the CNS. We hypothesized that RA is a regulator of the further differentiation of oligodendrocyte precursor cells (OPCs) - cells key to the remyelination process in MS. We conducted studies utilizing RNA-sequencing in human embryonic stem cell (hESC)-derived neural stem cells (NSCs) and OPCs so as to understand the role of transcriptional regulators during transition from both ESCs to NSCs and NSCs to OPCs...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29110207/ameliorating-effect-of-osteopontin-on-h2o2-induced-apoptosis-of-human-oligodendrocyte-progenitor-cells
#10
Neda Mazaheri, Maryam Peymani, Hamid Galehdari, Kamran Ghaedi, Ali Ghoochani, Abbas Kiani-Esfahani, Mohammad Hossein Nasr-Esfahani
Recently our group used oligodendrocyte progenitor cells (OPCs) as appropriate model cells to pinpoint the mechanism of the progress of neurodegenerative disorders. In the present study, we focused on the therapeutic role of osteopontin (OPN), a secreted glycosylated phosphoprotein, involved in a number of physiological events including bone formation and remodeling, immune responses, and tumor progression. Protective role of OPN, as a negative regulator of tumorigenesis, has already been clarified. Human embryonic stem cell-derived OPCs were pretreated with OPN before induction of apoptosis by H2O2...
November 6, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29081002/minocycline-directly-enhances-the-self-renewal-of-adult-neural-precursor-cells
#11
Anri Kuroda, Takahiro Fuchigami, Satoshi Fuke, Natsu Koyama, Kazuhiro Ikenaka, Seiji Hitoshi
Minocycline not only has antibacterial action but also produces a variety of pharmacological effects. It has drawn considerable attention as a therapeutic agent for symptoms caused by inflammation in many neurological disorders, leading to several clinical trials. Although some of these effects are mediated through its function of suppressing microglial activation, it is not clear whether minocycline acts on other cell types in the adult brain. In this study, we utilized a colony-forming neurosphere assay, in which neural stem cells (NSCs) clonally proliferate to form floating colonies, called neurospheres...
October 28, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29078813/the-trojan-horse-neuroinflammatory-impact-of-t-cells-in-neurodegenerative-diseases
#12
REVIEW
Annika Sommer, Beate Winner, Iryna Prots
Neuronal degeneration is a common mechanism of many neurological diseases including Parkinson's disease (PD), Alzheimer's disease (AD), and Multiple Sclerosis (MS). While AD and PD are classical neurodegenerative diseases, the primary pathology in MS is driven by autoimmune inflammation, attacking oligodendrocytes and thereby inducing neurodegeneration. In AD and PD, immune cells are also considered to play an important role in the disease progression. While the role of local central nervous system (CNS) innate immune cells is well described, a potential influence of adaptive immune cells in PD and AD is not yet fully understood...
October 27, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29065513/argan-oil-mediated-attenuation-of-organelle-dysfunction-oxidative-stress-and-cell-death-induced-by-7-ketocholesterol-in-murine-oligodendrocytes-158n
#13
Asmaa Badreddine, Amira Zarrouk, El Mostafa Karym, Meryam Debbabi, Thomas Nury, Wiem Meddeb, Randa Sghaier, Maryem Bezine, Anne Vejux, Lucy Martine, Stéphane Grégoire, Lionel Bretillon, Emmanuelle Prost-Camus, Philippe Durand, Michel Prost, Thibault Moreau, Mustapha Cherkaoui-Malki, Boubker Nasser, Gérard Lizard
Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects...
October 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28979206/cellular-pharmacological-effects-of-the-traditional-japanese-kampo-medicine-yokukansan-on-brain-cells
#14
REVIEW
Kazushige Mizoguchi, Yasushi Ikarashi
Yokukansan (YKS) is a traditional Japanese Kampo medicine currently used for the treatment of the behavioral psychological symptoms associated with dementia (BPSD), which is frequently problematic in neurodegenerative disorders such as Alzheimer's disease. Regarding the pharmacological mechanisms underlying its efficacy, we recently reviewed the multiple effects of YKS on the neurotransmitter systems (e.g., glutamatergic, serotonergic, dopaminergic, cholinergic, GABAergic, and adrenergic neurotransmission) in various brain regions that are related to the psychological, emotional, cognitive, or memory functions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28943274/gene-therapy-induced-antigen-specific-tregs-inhibit-neuro-inflammation-and-reverse-disease-in-a-mouse-model-of-multiple-sclerosis
#15
Geoffrey D Keeler, Sandeep Kumar, Brett Palaschak, Emily L Silverberg, David M Markusic, Noah T Jones, Brad E Hoffman
The devastating neurodegenerative disease multiple sclerosis (MS) could substantially benefit from an adeno-associated virus (AAV) immunotherapy designed to restore a robust and durable antigen-specific tolerance. However, developing a sufficiently potent and lasting immune-regulatory therapy that can intervene in ongoing disease is a major challenge and has thus been elusive. We addressed this problem by developing a highly effective and robust tolerance-inducing in vivo gene therapy. Using a pre-clinical animal model, we designed a liver-targeting gene transfer vector that expresses full-length myelin oligodendrocyte glycoprotein (MOG) in hepatocytes...
September 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28931570/mitochondrial-dna-double-strand-breaks-in-oligodendrocytes-cause-demyelination-axonal-injury-and-cns-inflammation
#16
Pernille M Madsen, Milena Pinto, Shreyans Patel, Stephanie McCarthy, Han Gao, Mehran Taherian, Shaffiat Karmally, Claudia V Pereira, Galina Dvoriantchikova, Dmitry Ivanov, Kenji F Tanaka, Carlos T Moraes, Roberta Brambilla
Mitochondrial dysfunction has been implicated in the pathophysiology of neurodegenerative disorders, including multiple sclerosis (MS). To date, the investigation of mitochondrial dysfunction in MS has focused exclusively on neurons, with no studies exploring whether dysregulation of mitochondrial bioenergetics and/or genetics in oligodendrocytes might be associated with the etiopathogenesis of MS and other demyelinating syndromes. To address this question, we established a mouse model where mitochondrial DNA (mtDNA) double-strand breaks (DSBs) were specifically induced in myelinating oligodendrocytes (PLP:mtPstI mice) by expressing a mitochondrial-targeted endonuclease, mtPstI, starting at 3 weeks of age...
October 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28911205/a-zebrafish-model-of-x-linked-adrenoleukodystrophy-recapitulates-key-disease-features-and-demonstrates-a-developmental-requirement-for-abcd1-in-oligodendrocyte-patterning-and-myelination
#17
Lauren R Strachan, Tamara J Stevenson, Briana Freshner, Matthew D Keefe, D Miranda Bowles, Joshua L Bonkowsky
X-linked adrenoleukodystrophy (ALD) is a devastating inherited neurodegenerative disease caused by defects in the ABCD1 gene and affecting peripheral and central nervous system myelin. ABCD1 encodes a peroxisomal transmembrane protein required for very long chain fatty acid (VLCFA) metabolism. We show that zebrafish (Danio rerio) Abcd1 is highly conserved at the amino acid level with human ABCD1, and during development is expressed in homologous regions including the central nervous system and adrenal glands...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28872660/fabricating-plga-microparticles-with-high-loads-of-the-small-molecule-antioxidant-n-acetylcysteine-that-rescue-oligodendrocyte-progenitor-cells-from-oxidative-stress
#18
Nicholas P Murphy, Kyle J Lampe
Reactive oxygen species (ROS), encompassing all oxygen radical or non-radical oxidizing agents, play key roles in disease progression. Controlled delivery of antioxidants is therapeutically relevant in such oxidant-stressed environments. Encapsulating small hydrophilic molecules into hydrophobic polymer microparticles via traditional emulsion methods has long been a challenge due to rapid mass transport of small molecules out of particle pores. We have developed a simple alteration to the existing water-in-oil-in-water (W/O/W) drug encapsulation method that dramatically improves loading efficiency: doping external water phases with drug to mitigate drug diffusion out of the particle during fabrication...
September 5, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28867896/neonatal-lipopolysaccharide-infection-causes-demyelination-and-behavioral-deficits-in-adult-and-senile-rat-brain
#19
Kavita Singh, Nisha Patro, M Pradeepa, Ishan Patro
BACKGROUND: Neonatal bacterial infections have been reported to cause white matter loss, although studies concerning the influence of infection on the expression of myelin and aging are still in their emerging state. PURPOSE: The present study aimed to investigate the effects of perinatal lipopolysaccharide (LPS) exposure on the myelination at different age points using histochemical and immunocytochemical techniques and the relative motor coordination. METHODS: A rat bacterial infection model was established by exposing the neonatal rats with LPS (0...
July 2017: Annals of Neurosciences
https://www.readbyqxmd.com/read/28867597/overexpression-of-suppressors-of-cytokine-signaling-1-regulate-the-proliferation-and-differentiation-of-rat-derived-neural-stem-cells
#20
Meng Cui, Xin-Long Ma, Jie Sun, Jin-Quan He, Lin Shen, Fang-Guo Li
Neural stem cells are a reliable resource in various neural tissue repair and neurodegenerative diseases. Increasing evidence has demonstrated that Suppressor of cytokine signaling proteins (SOCS) was involved in the nervous system development. The universality and diversity of SOCS also suggested their important roles in neurogenesis and nerve regeneration. In this study, we employed a lentiviral vector to investigate the impacts of overexpression SOCS1 on the proliferation and differentiation of rat-derived NSCs...
August 31, 2017: Acta Histochemica
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