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mTOR in neuron

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https://www.readbyqxmd.com/read/28323869/tyrosine-mutated-aav2-mediated-shrna-silencing-of-pten-promotes-axon-regeneration-of-adult-optic-nerve
#1
ZhengRu Huang, ZiZhong Hu, Ping Xie, QingHuai Liu
Activating PI3K/AKT/mTOR signaling pathway via deleting phosphatase and tensin homolog (PTEN) has been confirmed to enhance intrinsic growth capacity of neurons to facilitate the axons regeneration of central nervous system after injury. Considering conditional gene deletion is currently not available in clinical practice, we exploited capsid residue tyrosine 444 to phenylalanine mutated single-stranded adeno-associated virus serotype 2 (AAV2) as a vector delivering short hairpin RNA to silence PTEN to promote retinal ganglion cells (RGCs) survival and axons regeneration in adult rat optic nerve axotomy paradigm...
2017: PloS One
https://www.readbyqxmd.com/read/28317262/hydroxytyrosol-restores-proper-insulin-signaling-in-an-astrocytic-model-of-alzheimer-s-disease
#2
M Carmen Crespo, Joao Tomé-Carneiro, Cristina Pintado, Alberto Dávalos, Francesco Visioli, Emma Burgos-Ramos
Recent epidemiological evidence demonstrated that diabetes is a risk factor for AD onset and development. Indeed, meta-analyses of longitudinal epidemiologic studies show that diabetes increases AD risk by 50-100%, being insulin resistance (IR) the main binding link between diabetes and AD. Astrocytes are the foremost cerebral macroglial cells and are responsible for converting glucose into lactate and transfer it to neurons that use it as fuel, but Aβ(1-42) impairs insulin signaling and glycogen storage. Recent prospective studies showed that the Mediterranean diet is associated with lower incidence of AD...
March 20, 2017: BioFactors
https://www.readbyqxmd.com/read/28288862/autophagy-inhibits-c2-ceramide-mediated-cell-death-by-decreasing-the-reactive-oxygen-species-levels-in-sh-sy5y-cells
#3
Chenghe Fan, Yuanyuan Liu, Mingming Zhao, Rui Zhan, Wei Cui, Haiqiang Jin, Yuming Teng, Pu Lv, Lemin Zheng, Yining Huang
Ceramide has been recognized as a second messenger that regulates several intracellular processes in neuronal cells. However, its role in neuronal autophagy is not fully understood. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to investigate the mechanisms underlying C2-ceramide-mediated cell death and autophagy. C2-ceramide induced caspase-3-independent cell death. In addition, C2-ceramide induced autophagy, decreased the activation of Akt and mTOR, and increased the activation of JNK and ERK1/2...
March 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28287478/myocardial-ischemic-postconditioning-promotes-autophagy-against-ischemia-reperfusion-injury-via-the-activation-of-the-nnos-ampk-mtor-pathway
#4
Maojuan Hao, Suhua Zhu, Liang Hu, Hongyi Zhu, Xiaowei Wu, Qingping Li
Autophagy participates in the progression of many diseases, comprising ischemia/ reperfusion (I/R). It is reported that it is involved in the protective mechanism of ischemic postconditioning (IPostC). According to research, neuronal nitric oxide synthase (nNOS) is also involved in the condition of I/R and IPostC. However, the relationship between nNOS, autophagy and IPostC has not been previously investigated. We hypothesize that IPostC promotes autophagy activity against I/R injury partially through nNOS-mediated pathways...
March 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28273832/more-insight-into-bdnf-against-neurodegeneration-anti-apoptosis-anti-oxidation-and-suppression-of-autophagy
#5
REVIEW
Shang-Der Chen, Chia-Lin Wu, Wei-Chao Hwang, Ding-I Yang
In addition to its well-established neurotrophic action, brain-derived neurotrophic factor (BDNF) also possesses other neuroprotective effects including anti-apoptosis, anti-oxidation, and suppression of autophagy. We have shown before that BDNF triggers multiple mechanisms to confer neuronal resistance against 3-nitropropionic acid (3-NP)-induced mitochondrial dysfunction in primary rat cortical cultures. The beneficial effects of BDNF involve the induction of anti-oxidative thioredoxin with the resultant expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) as well as erythropoietin (EPO)-dependent stimulation of sonic hedgehog (SHH)...
March 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28260507/tanshinone-iia-protects-hippocampal-neuronal-cells-from-reactive-oxygen-species-through-changes-in-autophagy-and-activation-of-phosphatidylinositol-3-kinase-protein-kinas-b-and-mechanistic-target-of-rapamycin-pathways
#6
Ruodong Han, Guopin Wang, Qiqiang Tang, Yingchun Zhu
BACKGROUND: Tanshinone IIA is a key active ingredient of danshen, which derived from the dried root or rhizome of Salviae miltiorrhizae Bge. The tanshinone IIA has protective effects against focal cerebral ischemic injury. However, the underlying mechanisms remain unclear. METHODS: An in vitro model of cerebral ischemia was established by subjecting cultures of hippocampal neuronal cells to oxygen-glucose deprivation followed by reperfusion (OGD/R). The probes of 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) and 5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine,iodide (JC-1) were used to determine the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production...
March 5, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28250148/mtor-regulates-peripheral-nerve-response-to-tensile-strain
#7
James M Love, Brian G Bober, Elisabeth Orozco, Amanda T White, Shannon N Bremner, Richard M Lovering, Simon Schenk, Sameer B Shah
While excessive tensile strain can be detrimental to nerve function, strain can be a positive regulator of neuronal outgrowth. We used an in vivo rat model of sciatic nerve strain to investigate signaling mechanisms underlying peripheral nerve response to deformation. Nerves were deformed by 11%, and did not demonstrate deficits in compound action potential latency or amplitude during or after 6 hours of strain. As revealed by Western blotting, application of strain resulted in significant upregulation of mammalian target of rapamycin (mTOR) and S6 signaling in nerves, increased myelin basic protein (MBP) and β-actin levels, and increased phosphorylation of neurofilament subunit H (NF-H) compared to unstrained (sham) contralateral nerves (p < 0...
March 1, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28242433/the-tired-hippocampus-the-molecular-impact-of-sleep-deprivation-on-hippocampal-function
#8
REVIEW
Robbert Havekes, Ted Abel
Memory consolidation, the process by which information is stored following training, consists of synaptic consolidation and systems consolidation. It is widely acknowledged that sleep deprivation has a profound effect on synaptic consolidation, particularly for memories that require the hippocampus. It is unclear, however, which of the many molecular changes associated with sleep deprivation directly contribute to memory deficits. In this review, we highlight recent studies showing that sleep deprivation impairs hippocampal cAMP and mTOR signaling, and ultimately causes spine loss in CA1 neurons in a cofilin-dependent fashion...
February 27, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28215400/somatic-mutations-in-tsc1-and-tsc2-cause-focal-cortical-dysplasia
#9
Jae Seok Lim, Ramu Gopalappa, Se Hoon Kim, Suresh Ramakrishna, Minji Lee, Woo-Il Kim, Junho Kim, Sang Min Park, Junehawk Lee, Jung-Hwa Oh, Heung Dong Kim, Chang-Hwan Park, Joon Soo Lee, Sangwoo Kim, Dong Seok Kim, Jung Min Han, Hoon-Chul Kang, Hyongbum Henry Kim, Jeong Ho Lee
Focal cortical dysplasia (FCD) is a major cause of the sporadic form of intractable focal epilepsies that require surgical treatment. It has recently been reported that brain somatic mutations in MTOR account for 15%-25% of FCD type II (FCDII), characterized by cortical dyslamination and dysmorphic neurons. However, the genetic etiologies of FCDII-affected individuals who lack the MTOR mutation remain unclear. Here, we performed deep hybrid capture and amplicon sequencing (read depth of 100×-20,012×) of five important mTOR pathway genes-PIK3CA, PIK3R2, AKT3, TSC1, and TSC2-by using paired brain and saliva samples from 40 FCDII individuals negative for MTOR mutations...
March 2, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28214828/role-for-target-of-rapamycin-mtor-signal-pathway-in-regulating-neuronal-injury-after-intracerebral-hemorrhage
#10
Jie-Ping Wang, Meng-Yu Zhang
BACKGROUND/AIMS: Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR signal and its downstream products to brain injuries induced by intracerebral hemorrhage (ICH) in rats. METHODS: Western Blot analysis was employed to examine the protein expression of mTOR and its downstream pathway and Caspase-3...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28192065/vascular-endothelial-growth-factor-a-and-leptin-expression-associated-with-ectopic-proliferation-and-retinal-dysplasia-in-zebrafish-optic-pathway-tumors
#11
Laura E Schultz, Staci L Solin, Wesley A Wierson, Janna M Lovan, Judith Syrkin-Nikolau, Deborah E Lincow, Andrew J Severin, Donald S Sakaguchi, Maura McGrail
In the central nervous system injury induces cellular reprogramming and progenitor proliferation, but the molecular mechanisms that limit regeneration and prevent tumorigenesis are not completely understood. We previously described a zebrafish optic pathway tumor model in which transgenic Tg(flk1:RFP)is18/+ adults develop nonmalignant retinal tumors. Key pathways driving injury-induced glial reprogramming and regeneration contributed to tumor formation. In this study, we examine a time course of proliferation and present new analyses of the Tg(flk1:RFP)is18/+ dysplastic retina and tumor transcriptomes...
February 13, 2017: Zebrafish
https://www.readbyqxmd.com/read/28188143/statement-of-retraction-a-central-role-for-neuronal-amp-activated-protein-kinase-ampk-and-mammalian-target-of-rapamycin-mtor-in-high-protein-diet-induced-weight-loss-diabetes-2008-57-594-605-doi-10-2337-db07-0573
#12
Eduardo R Ropelle, José R Pauli, Maria Fernanda A Fernandes, Silvana A Rocco, Rodrigo M Marin, Joseane Morari, Kellen K Souza, Marília M Dias, Maria C Gomes-Marcondes, José A R Gontijo, Kleber G Franchini, Lício A Velloso, Mario J A Saad, José B C Carvalheira
No abstract text is available yet for this article.
2017: Diabetes
https://www.readbyqxmd.com/read/28186165/netrin-1-improves-functional-recovery-through-autophagy-regulation-by-activating-the-ampk-mtor-signaling-pathway-in-rats-with-spinal-cord-injury
#13
Liangjie Bai, Xifan Mei, Zhaoliang Shen, Yunlong Bi, Yajiang Yuan, Zhanpeng Guo, Hongyu Wang, Haosen Zhao, Zipeng Zhou, Chen Wang, Kunming Zhu, Gang Li, Gang Lv
Autophagy is an process for the degradation of cytoplasmic aggregated proteins and damaged organelles and plays an important role in the development of SCI. In this study, we investigated the therapeutic effect of Netrin-1 and its potential mechanism for autophagy regulation after SCI. A rat model of SCI was established and used for analysis. Results showed that administration of Netrin-1 not only significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK) but also reduced the phosphorylation of mammalian target of rapamycin (mTOR) and P70S6K...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28183735/new-insights-into-the-regulatory-function-of-cyfip1-in-the-context-of-wave-and-fmrp-containing-complexes
#14
Sabiha Abekhoukh, H Bahar Sahin, Mauro Grossi, Samantha Zongaro, Thomas Maurin, Irene Madrigal, Daniele Kazue-Sugioka, Annick Raas-Rothschild, Mohamed Doulazmi, Pilar Carrera, Andrea Stachon, Steven Scherer, Maria Rita Drula Do Nascimento, Alain Trembleau, Ignacio Arroyo, Szatmari Peter, Isabel M Smith, Montserrat Milà, Adam C Smith, Angela Giangrande, Isabelle Caillé, Barbara Bardoni
CYtoplasmic FMRP Interacting Protein 1 (CYFIP1) is a candidate gene for intellectual disability (ID), autism, schizophrenia and epilepsy. It is a member of a family of proteins that is very conserved during evolution, sharing high homology with dCYFIP, its Drosophila homolog. CYFIP1 interacts with the Fragile X Mental Retardation Protein (FMRP), whose absence causes the Fragile X Syndrome, and with the translation initiation factor eIF4E. It is a member of the WAVE Regulatory Complex (WRC), thus representing a link between translational regulation and actin cytoskeleton...
February 9, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28183733/neuronal-ctgf-ccn2-negatively-regulates-myelination-in-a-mouse-model-of-tuberous-sclerosis-complex
#15
Ebru Ercan, Juliette M Han, Alessia Di Nardo, Kellen Winden, Min-Joon Han, Leonie Hoyo, Afshin Saffari, Andrew Leask, Daniel H Geschwind, Mustafa Sahin
Disruption of myelination during development has been implicated in a range of neurodevelopmental disorders including tuberous sclerosis complex (TSC). TSC patients with autism display impairments in white matter integrity. Similarly, mice lacking neuronal Tsc1 have a hypomyelination phenotype. However, the mechanisms that underlie these phenotypes remain unknown. In this study, we demonstrate that neuronal TSC1/2 orchestrates a program of oligodendrocyte maturation through the regulated secretion of connective tissue growth factor (CTGF)...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28181071/neurotrophic-effect-of-asiatic-acid-a-triterpene-of-centella-asiatica-against-chronic-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-hydrochloride-probenecid-mouse-model-of-parkinson-s-disease-the-role-of-mapk-pi3k-akt-gsk3%C3%AE-and-mtor-signalling-pathways
#16
Jagatheesan Nataraj, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa
Regulation of various signalling (Ras-MAPK, PI3K and AKT) pathways by augmented activity of neurotrophic factors (NTFs) could prevent or halt the progress of dopaminergic loss in Parkinson's disease (PD). Various in vitro and in vivo experimental studies indicated anti-parkinsonic potential of asiatic acid (AA), a pentacyclic triterpene obtained from Centella asiatica. So the present study is designed to determine the neurotrophic effect of AA against 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine hydrochloride/probenecid (MPTP/p) neurotoxicity in mice model of PD...
February 8, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28177899/mtor-autophagy-pathway-in-the-hippocampus-of-rats-suffering-intermittent-hypoxia-preconditioning-and-global-cerebral-ischemia-reperfusion
#17
Ya-Ning Zhao, Xiang-Fei Guo, Jian-Min Li, Chang-Xiang Chen, Shu-Xing Li, Cheng-Jing Xu
We explored the role of mTOR/autophagy pathway in the aggravation of cerebral ischemia-reperfusion nerve injury caused by intermittent hypoxia. Eighty male wistar rats were divided into four groups by the random number method: sham operation group (SO group, n=20), cerebral ischemia-reperfusion group (I/R group, n=20), intermittent hypoxia and cerebral ischemia-reperfusion group (IH+I/R group, n=20), intermittent hypoxia and cerebral ischemia-reperfusion group plus mTOR inhibitor group (inhibitor group, n=20)...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28148781/the-amino-acid-metabolite-homocysteine-activates-mtorc1-to-inhibit-autophagy-and-form-abnormal-proteins-in-human-neurons-and-mice
#18
Khoosheh Khayati, Henri Antikainen, Edward M Bonder, Gregory F Weber, Warren D Kruger, Hieronim Jakubowski, Radek Dobrowolski
The molecular mechanisms leading to and responsible for age-related, sporadic Alzheimer's disease (AD) remain largely unknown. It is well documented that aging patients with elevated levels of the amino acid metabolite homocysteine (Hcy) are at high risk of developing AD. We investigated the impact of Hcy on molecular clearance pathways in mammalian cells, including in vitro cultured induced pluripotent stem cell-derived forebrain neurons and in vivo neurons in mouse brains. Exposure to Hcy resulted in up-regulation of the mechanistic target of rapamycin complex 1 (mTORC1) activity, one of the major kinases in cells that is tightly linked to anabolic and catabolic pathways...
February 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28143498/neuroprotective-effects-of-intrastriatal-injection-of-rapamycin-in-a-mouse-model-of-excitotoxicity-induced-by-quinolinic-acid
#19
Soraya Wilke Saliba, Erica Leandro Marciano Vieira, Rebeca Priscila de Melo Santos, Eduardo Candelario-Jalil, Bernd L Fiebich, Luciene Bruno Vieira, Antonio Lucio Teixeira, Antonio Carlos Pinheiro de Oliveira
BACKGROUND: The mammalian target of rapamycin (mTOR) is a kinase involved in a variety of physiological and pathological functions. However, the exact role of mTOR in excitotoxicity is poorly understood. Here, we investigated the effects of mTOR inhibition with rapamycin against neurodegeneration, and motor impairment, as well as inflammatory profile caused by an excitotoxic stimulus. METHODS: A single and unilateral striatal injection of quinolinic acid (QA) was used to induce excitotoxicity in mice...
January 31, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28137967/selenomethionine-mitigates-cognitive-decline-by-targeting-both-tau-hyperphosphorylation-and-autophagic-clearance-in-an-alzheimer-s-disease-mouse-model
#20
Zhong-Hao Zhang, Qiu-Yan Wu, Rui Zheng, Chen Chen, Yao Chen, Qiong Liu, Peter R Hoffmann, Jia-Zuan Ni, Guo-Li Song
Tau pathology was recently identified as a key driver of disease progression and an attractive therapeutic target in Alzheimer's disease (AD). Selenomethionine (Se-Met), a major bioactive form of selenium (Se) in organisms with significant antioxidant capacity, reduced the levels of total tau and hyperphosphorylated tau and ameliorated cognitive deficits in younger triple transgenic AD (3xTg-AD) mice. Whether Se-Met has a similar effect on tau pathology and the specific mechanism of action in older 3xTg-AD mice remains unknown...
January 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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