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Neurotrophin production

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https://www.readbyqxmd.com/read/28761415/dual-and-multi-drug-delivery-nanoparticles-towards-neuronal-survival-and-synaptic-repair
#1
REVIEW
Angelina Angelova, Borislav Angelov
Among the macromolecular drug targets in neurodegenerative disorders, the neurotrophin brain-derived neurotrophic factor (BDNF) and its high-affinity tropomyosin-related kinase receptor (TrkB) present strong interest for nanomedicine development aiming at neuronal and synaptic repair. Currently, BDNF is regarded as the neurotrophic factor of highest therapeutic significance. However, BDNF has delivery problems as a protein drug. The enhanced activation of the transcription factor CREB (cAMP response element-binding protein) has been evidenced to increase the BDNF gene expression and hence the production of endogenous BDNF...
June 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28725180/endothelial-nitric-oxide-synthase-is-present-in-dendritic-spines-of-neurons-in-primary-cultures
#2
Ariel Caviedes, Manuel Varas-Godoy, Carlos Lafourcade, Soledad Sandoval, Javiera Bravo-Alegria, Thilo Kaehne, Angela Massmann, Jorge P Figueroa, Francisco Nualart, Ursula Wyneken
Nitric oxide exerts important regulatory functions in various brain processes. Its synthesis in neurons has been most commonly ascribed to the neuronal nitric oxide synthase (nNOS) isoform. However, the endothelial isoform (eNOS), which is significantly associated with caveolae in different cell types, has been implicated in synaptic plasticity and is enriched in the dendrites of CA1 hippocampal neurons. Using high resolution microscopy and co-distribution analysis of eNOS with synaptic and raft proteins, we now show for the first time in primary cortical and hippocampal neuronal cultures, virtually devoid of endothelial cells, that eNOS is present in neurons and is localized in dendritic spines...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28606778/hmgb1-promotes-neurovascular-remodeling-via-rage-in-the-late-phase-of-subarachnoid-hemorrhage
#3
Xiaodi Tian, Liang Sun, Dongxia Feng, Qing Sun, Yang Dou, Chenglin Liu, Feng Zhou, Haiying Li, Haitao Shen, Zhong Wang, Gang Chen
High-mobility group box1 (HMGB1) is a nuclear protein widely expressed in the central nervous system. Extracellular HMGB1 serves as a proinflammatory cytokine and contributes to brain injury during the acute stage post-stroke. Recently, increasing evidence has demonstrated beneficial effects of HMGB1 in some types of brain injury, but little is known about its effects during the late phase of subarachnoid hemorrhage (SAH). This study was designed to explore the potential roles and mechanisms of HMGB1 and its receptor, receptor for advanced glycation end-products (Rage), on brain recovery in the late stage of experimental SAH...
June 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28604632/experimental-autoimmune-encephalomyelitis-eae-induced-elevated-expression-of-the-e1-isoform-of-methyl-cpg-binding-protein-2-mecp2e1-implications-in-multiple-sclerosis-ms-induced-neurological-disability-and-associated-myelin-damage
#4
Tina Khorshid Ahmad, Ting Zhou, Khaled AlTaweel, Claudia Cortes, Ryan Lillico, Ted Martin Lakowski, Kiana Gozda, Michael Peter Namaka
Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression...
June 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28601428/vegf-production-and-signaling-in-m%C3%A3-ller-glia-are-critical-to-modulating-vascular-function-and-neuronal-integrity-in-diabetic-retinopathy-and-hypoxic-retinal-vascular-diseases
#5
Yun-Zheng Le
Müller glia (MG) are major retinal supporting cells that participate in retinal metabolism, function, maintenance, and protection. During the pathogenesis of diabetic retinopathy (DR), a neurovascular disease and a leading cause of blindness, MG modulate vascular function and neuronal integrity by regulating the production of angiogenic and trophic factors. In this article, I will (1) briefly summarize our work on delineating the role and mechanism of MG-modulated vascular function through the production of vascular endothelial growth factor (VEGF) and on investigating VEGF signaling-mediated MG viability and neural protection in diabetic animal models, (2) explore the relationship among VEGF and neurotrophins in protecting Müller cells in in vitro models of diabetes and hypoxia and its potential implication to neuroprotection in DR and hypoxic retinal diseases, and (3) discuss the relevance of our work to the effectiveness and safety of long-term anti-VEGF therapies, a widely used strategy to combat DR, diabetic macular edema, neovascular age-related macular degeneration, retinopathy of prematurity, and other hypoxic retinal vascular disorders...
June 21, 2017: Vision Research
https://www.readbyqxmd.com/read/28559796/presynaptic-membrane-receptors-modulate-ach-release-axonal-competition-and-synapse-elimination-during-neuromuscular-junction-development
#6
REVIEW
Josep Tomàs, Neus Garcia, Maria A Lanuza, Manel M Santafé, Marta Tomàs, Laura Nadal, Erica Hurtado, Anna Simó, Víctor Cilleros
During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ) are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28542352/preconditioning-of-adipose-tissue-derived-mesenchymal-stem-cells-with-deferoxamine-increases-the-production-of-pro-angiogenic-neuroprotective-and-anti-inflammatory-factors-potential-application-in-the-treatment-of-diabetic-neuropathy
#7
Carolina Oses, Belén Olivares, Marcelo Ezquer, Cristian Acosta, Paul Bosch, Macarena Donoso, Patricio Léniz, Fernando Ezquer
Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors...
2017: PloS One
https://www.readbyqxmd.com/read/28537420/nitration-and-glycation-turn-mature-ngf-into-a-toxic-factor-for-motor-neurons-a-role-for-p75-sup-ntr-sup-and-rage-signaling-in-als
#8
Mi Jin Kim, Marcelo R Vargas, Benjamin A Harlan, Kelby M Killoy, Lauren Ball, Susana Comte-Walters, Monika Gooz, Yasuhiko Yamamoto, Joseph S Beckman, Luis Barbeito, Mariana Pehar
Glycating stress can occur together with oxidative stress during neurodegeneration and contribute to the pathogenic mechanism. Nerve growth factor (NGF) accumulates in several neurodegenerative diseases. Besides promoting survival, NGF can paradoxically induce cell death by signaling through the p75 neurotrophin receptor (p75<sup>NTR</sup>). The ability of NGF to induce cell death is increased by nitration of its tyrosine residues under conditions associated with increased peroxynitrite formation...
May 24, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28529157/protective-treatments-and-their-target-retinal-ganglion-cells-in-diabetic-retinopathy
#9
REVIEW
Jing Zhang, Rong Liu, Hong-Yu Kuang, Xin-Yuan Gao, Hao-Ling Liu
Diabetic retinopathy(DR)is one of the complications of diabetes which could cause severe vision loss. Retinal ganglion cell(RGC)injury has been confirmed prior to micro-vascular damage. Over the past few decades, a number of animal and clinical studies have confirmed that RGC impairment leads to an early deterioration of vision in DR. Inhibition of aldose reductase (AR), advanced glycation end product (AGE), oxidative stress, glutamate toxicity, and an inflammatory response may play important roles in protecting RGCs in DR...
June 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28506823/hyperammonemia-compromises-glutamate-metabolism-and-reduces-bdnf-in-the-rat-hippocampus
#10
Fabiana Galland, Elisa Negri, Carollina Da Ré, Fernanda Fróes, Liliane Strapazzon, Maria Cristina Guerra, Lucas Silva Tortorelli, Carlos-Alberto Gonçalves, Marina Concli Leite
Ammonia is putatively the major toxin associated with hepatic encephalopathy (HE), a neuropsychiatric manifestation that results in cognitive impairment, poor concentration and psychomotor alterations. The hippocampus, a brain region involved in cognitive impairment and depressive behavior, has been studied less than neocortical regions. Herein, we investigated hippocampal astrocyte parameters in a hyperammonemic model without hepatic lesion and in acute hippocampal slices exposed to ammonia. We also measured hippocampal BDNF, a neurotrophin commonly related to synaptic plasticity and cognitive deficit, and peripheral S100B protein, used as a marker for brain damage...
May 12, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28505381/insulin-resistance-disrupts-the-interaction-between-akt-and-the-nmda-receptor-and-the-inactivation-of-the-camkiv-creb-pathway-in-minimal-hepatic-encephalopathy
#11
Saidan Ding, Weishan Zhuge, Jianjing Yang, Fangfang Wen, Zhu Xu, Xuebao Wang, Qichuan Zhuge
Hepatic cirrhosis-induced Minimal hepatic encephalopathy (MHE) has been characterized for cognitive dysfunction and central nervous system (CNS) insulin resistance (IR) has been acknowledged to be closely correlated with cognitive impairment while hepatic cirrhosis has been recognized to induce IR . Thus, this study aimed to investigate whether CNS IR occurred in MHE and induced MHE, as well as the underlying mechanism. We found IR in the MHE rats, an especially decreased level of the insulin receptor (InsR), and an increased serine phosphorylation of IRS1 in CNS...
May 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28498321/bdnf-binds-its-pro-peptide-with-high-affinity-and-the-common-val66met-polymorphism-attenuates-the-interaction
#12
Koichi Uegaki, Haruko Kumanogoh, Toshiyuki Mizui, Takatsugu Hirokawa, Yasuyuki Ishikawa, Masami Kojima
Most growth factors are initially synthesized as precursors then cleaved into bioactive mature domains and pro-domains, but the biological roles of pro-domains are poorly understood. In the present study, we investigated the pro-domain (or pro-peptide) of brain-derived neurotrophic factor (BDNF), which promotes neuronal survival, differentiation and synaptic plasticity. The BDNF pro-peptide is a post-processing product of the precursor BDNF. Using surface plasmon resonance and biochemical experiments, we first demonstrated that the BDNF pro-peptide binds to mature BDNF with high affinity, but not other neurotrophins...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28466111/use-of-brevibacillus-choshinensis-for-the-production-of-biologically-active-brain-derived-neurotrophic-factor-bdnf
#13
Phillip A Angart, Rebecca J Carlson, Sarah Thorwall, S Patrick Walton
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family critical for neuronal cell survival and differentiation, with therapeutic potential for the treatment of neurological disorders and spinal cord injuries. The production of recombinant, bioactive BDNF is not practical in most traditional microbial expression systems because of the inability of the host to correctly form the characteristic cystine-knot fold of BDNF. Here, we investigated Brevibacillus choshinensis as a suitable expression host for bioactive BDNF expression, evaluating the effects of medium type (2SY and TM), temperature (25 and 30 °C), and culture time (48-120 h)...
May 2, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28440798/improved-gene-delivery-to-adult-mouse-spinal-cord-through-the-use-of-engineered-hybrid-adeno-associated-viral-serotypes
#14
J J Siu, N J Queen, W Huang, F Q Yin, X Liu, C Wang, D M McTigue, L Cao
Adeno-associated viral (AAV) vectors are often used in gene therapy for neurological disorders because of its safety profile and promising results in clinical trials. One challenge to AAV gene therapy is effective transduction of large numbers of the appropriate cell type, which can be overcome by modulating the viral capsid through DNA shuffling. Our previous study demonstrates that Rec2, among a family of novel engineered hybrid capsid serotypes (Rec1~4) transduces adipose tissue with far superior efficiency than naturally occurring AAV serotypes...
June 2017: Gene Therapy
https://www.readbyqxmd.com/read/28418861/brain-derived-neurotrophic-factor-involved-epigenetic-repression-of-ugt2b7-in-colorectal-carcinoma-a-mechanism-to-alter-morphine-glucuronidation-in-tumor
#15
Zi-Zhao Yang, Li Li, Ming-Cheng Xu, Hai-Xing Ju, Miao Hao, Jing-Kai Gu, Zai-Jie Jim Wang, Hui-Di Jiang, Lu-Shan Yu, Su Zeng
Uridine diphosphate-glucuronosyltransferase (UGT) 2B7, as one of significant drug enzymes, is responsible on the glucuronidation of abundant endobiotics or xenobiotics. We here report that it is markedly repressed in the tumor tissues of colorectal carcinoma (CRC) patients. Accordingly, morphine in CRC cells will stimulate the expression of its main metabolic enzyme, UGT2B7 during tolerance generation by activating the positive signals in histone 3, especially for trimethylated lysine 27 (H3K4Me3) and acetylated lysine 4 (H3K27Ac)...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404842/an-immortalized-human-dorsal-root-ganglion-cell-line-provides-a-novel-context-to-study-herpes-simplex-virus-1-latency-and-reactivation
#16
Nikki M Thellman, Carolyn Botting, Zachary Madaj, Steven J Triezenberg
A defining characteristic of alphaherpesviruses is the establishment of lifelong latency in host sensory ganglia with occasional reactivation causing recurrent lytic infections. As an alternative to rodent models, we explored the use of an immortalized cell line derived from human dorsal root ganglia. HD10.6 cells proliferate by virtue of a transduced tetracycline-regulated v-myc oncogene. In the presence of doxycycline, HD10.6 cells mature to exhibit neuronal morphology and express sensory neuron-associated markers such as neurotrophin receptors TrkA, TrkB, TrkC, and RET and the sensory neurofilament peripherin...
June 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28392360/matrine-promotes-nt3-expression-in-cns-cells-in-experimental-autoimmune-encephalomyelitis
#17
Ming-Liang Zhang, Xiao-Jian Zhang, Jian Kang, Hui-Jun Zhang, Xiao-Long Chen, Nan Liu, Shu-Qing Liu, Wen-Di Ma, Guang-Xian Zhang, Lin Zhu
Neurotrophin 3 (NT3) is a potent neurotrophic factor for promoting remyelination and recovery of neuronal function; upregulation of its expression in the central nervous system (CNS) is thus of major therapeutic importance for neurological deficits. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flavescent, has been recently reported to effectively ameliorate clinical signs in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by secreting antiinflammatory cytokines...
April 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28356268/neurotrophin-3-upregulates-proliferation-and-collagen-production-in-human-aortic-valve-interstitial-cells-a-potential-role-in-aortic-valve-sclerosis
#18
Qingzhou Yao, Rui Song, Lihua Ao, Joseph C Cleveland, David A Fullerton, Xianzhong Meng
Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves overexpress growth factor neurotrophin 3 (NT3)...
June 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28347717/long-non-coding-rnas-in-brain-development-synaptic-biology-and-alzheimer-s-disease
#19
REVIEW
Changhua Shi, Ling Zhang, Chuan Qin
Long non-coding RNAs (lncRNAs), which are long transcripts without apparent protein-coding roles, interfere with gene expression and signaling events at various stages. Increasing evidence has suggested that lncRNAs function in the regulation of tissue homeostasis and under pathophysiologic conditions. In the nervous system, the expression of lncRNAs has been detected and characterized under normal physiologic conditions and in disease states. Some lncRNAs regulate brain development and synaptic plasticity...
June 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28337122/cerebrospinal-fluid-cortisol-mediates-brain-derived-neurotrophic-factor-relationships-to-mortality-after-severe-tbi-a-prospective-cohort-study
#20
Miranda J Munoz, Raj G Kumar, Byung-Mo Oh, Yvette P Conley, Zhensheng Wang, Michelle D Failla, Amy K Wagner
Distinct regulatory signaling mechanisms exist between cortisol and brain derived neurotrophic factor (BDNF) that may influence secondary injury cascades associated with traumatic brain injury (TBI) and predict outcome. We investigated concurrent CSF BDNF and cortisol relationships in 117 patients sampled days 0-6 after severe TBI while accounting for BDNF genetics and age. We also determined associations between CSF BDNF and cortisol with 6-month mortality. BDNF variants, rs6265 and rs7124442, were used to create a gene risk score (GRS) in reference to previously published hypothesized risk for mortality in "younger patients" (<48 years) and hypothesized BDNF production/secretion capacity with these variants...
2017: Frontiers in Molecular Neuroscience
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