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mTOR in neuron

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https://www.readbyqxmd.com/read/28434145/mtorc1-signaling-in-hepatic-lipid-metabolism
#1
REVIEW
Jinbo Han, Yiguo Wang
The mechanistic target of rapamycin (mTOR) signaling pathway regulates many metabolic and physiological processes in different organs or tissues. Dysregulation of mTOR signaling has been implicated in many human diseases including obesity, diabetes, cancer, fatty liver diseases, and neuronal disorders. Here we review recent progress in understanding how mTORC1 (mTOR complex 1) signaling regulates lipid metabolism in the liver.
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28421530/time-of-day-dependent-neuronal-injury-after-ischemic-stroke-implication-of-circadian-clock-transcriptional-factor-bmal1-and-survival-kinase-akt
#2
Mustafa Caglar Beker, Berrak Caglayan, Esra Yalcin, Ahmet Burak Caglayan, Seyma Turkseven, Busra Gurel, Taha Kelestemur, Elif Sertel, Zafer Sahin, Selim Kutlu, Ulkan Kilic, Ahmet Tarik Baykal, Ertugrul Kilic
Occurrence of stroke cases displays a time-of-day variation in human. However, the mechanism linking circadian rhythm to the internal response mechanisms against pathophysiological events after ischemic stroke remained largely unknown. To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R) injury were investigated in mice in which the ischemic stroke induced at four different Zeitgeber time points with 6-h intervals (ZT0, ZT6, ZT12, and ZT18). Besides infarct volume and brain swelling, neuronal survival, apoptosis, ischemia, and circadian rhythm related proteins were examined using immunohistochemistry, Western blot, planar surface immune assay, and liquid chromatography-mass spectrometry tools...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28418837/rapamycin-promotes-differentiation-increasing-%C3%AE-iii-tubulin-neun-and-neurod-while-suppressing-nestin-expression-in-glioblastoma-cells
#3
Michela Ferrucci, Francesca Biagioni, Paola Lenzi, Stefano Gambardella, Rosangela Ferese, Maria Teresa Calierno, Alessandra Falleni, Alfonso Grimaldi, Alessandro Frati, Vincenzo Esposito, Cristina Limatola, Francesco Fornai
Glioblastoma cells feature mammalian target of rapamycin (mTOR) up-regulation which relates to a variety of effects such as: lower survival, higher infiltration, high stemness and radio- and chemo-resistance. Recently, it was demonstrated that mTOR may produce a gene shift leading to altered protein expression. Therefore, in the present study we administered different doses of the mTOR inhibitor rapamycin to explore whether the transcription of specific genes are modified. By using a variety of methods we demonstrate that rapamycin stimulates gene transcription related to neuronal differentiation while inhibiting stemness related genes such as nestin...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401012/nrsn2-promotes-osteosarcoma-cell-proliferation-and-growth-through-pi3k-akt-mtor-and-wnt-%C3%AE-catenin-signaling
#4
Ajimu Keremu, Xiayimaierdan Maimaiti, Abudusaimi Aimaiti, Maimaiaili Yushan, Yamuhanmode Alike, Yilizati Yilihamu, Aihemaitijiang Yusufu
Osteosarcoma is the most common bone cancer in children and adults. However, its pathogenesis, especially molecular mechanisms remain elusive. In current study, we screened GEO Database and found a poorly studied protein Neurensin-2 (NRSN2), which is highly expressed in osteosarcoma tissues. Neurensin-2 (NRSN2) is a small neuronal membrane protein and localized in small vesicles in neural cells, previous study found that it has been implicated in hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC)...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28399115/neonatal-mouse-hippocampus-phlebotomy-induced-anemia-diminishes-and-treatment-with-erythropoietin-partially-rescues-mammalian-target-of-rapamycin-mtor-signaling
#5
Diana J Wallin, Tara G Zamora, Michelle Alexander, Kathleen M Ennis, Phu V Tran, Michael K Georgieff
BACKGROUND: Phlebotomy-induced anemia (PIA) is common in premature infants and affects neurodevelopment. PIA alters hippocampal metabolism in neonatal mice through tissue hypoxia and iron deficiency. The mammalian target of rapamycin (mTOR) pathway senses the status of critical metabolites (e.g., oxygen, iron), thereby regulating hippocampal growth and function. We determined the effect of PIA and recombinant human erythropoietin (rHuEpo) treatment on mTOR signaling and expression of genes related to mTOR pathway functions...
April 11, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28396174/sirt3-confers-protection-against-neuronal-ischemia-by-inducing-autophagy-involvement-of-the-ampk-mtor-pathway
#6
Shu-Hui Dai, Tao Chen, Xia Li, Kang-Yi Yue, Peng Luo, Li-Kun Yang, Jie Zhu, Yu-Hai Wang, Zhou Fei, Xiao-Fan Jiang
Sirtuin3 (Sirt3) is a member of the silent information regulator 2 (Sir2) family of proteins located in mitochondria that influences almost every major aspect of mitochondrial biology, including ATP generation and reactive oxygen species (ROS) production. Our previous study showed that Sirt3 exerts protective effects against oxidative stress in neuronal cells. In this study, we investigated the role of Sirt3 in neuronal ischemia using an oxygen and glucose deprivation (OGD) model. Sirt3 was up-regulated by OGD and overexpression of Sirt3 through lentivirus transfection significantly reduced OGD-induced lactate dehydrogenase (LDH) release and neuronal apoptosis...
April 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28395287/interleukin-1%C3%AE-plays-a-pivotal-role-via-the-pi3k-akt-mtor-signaling-pathway-in-the-chronicity-of-mesial-temporal-lobe-epilepsy
#7
Zhaohua Xiao, Jing Peng, Na Gan, Ahmed Arafat, Fei Yin
OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is the most common type of refractory epilepsy. It is often associated with hippocampal sclerosis, which is histopathologically characterized by selective neuron loss, mossy fiber sprouting, and synapse reconstruction, and is the primary cause of refractory epilepsy. Its mechanism has not been fully elucidated. Substantial evidence now supports that inflammatory pathways are activated in epilepsy foci. We have confirmed that the interleukin-1β (IL-1β) level is involved in the epileptogenesis of MTLE, and we further investigated how it works in its chronicity in this study...
April 11, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28390940/ginkgo-biloba-l-attenuates-spontaneous-recurrent-seizures-and-associated-neurological-conditions-in-lithium-pilocarpine-rat-model-of-temporal-lobe-epilepsy-through-inhibition-of-mammalian-target-of-rapamycin-pathway-hyperactivation
#8
Arindam Ghosh Mazumder, Pallavi Sharma, Vikram Patial, Damanpreet Singh
ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. (Ginkgoaceae) has been widely used in traditional medicine for variety of neurological conditions particularly behavioral and memory impairments. AIM OF THE STUDY: The present study was envisaged to explore the effect of a standardized fraction of Ginkgo biloba leaves (GBbf) in rat model of lithium-pilocarpine induced spontaneous recurrent seizures, and associated behavioral impairments and cognitive deficit. MATERIALS AND METHODS: Rats showing appearance of spontaneous recurrent seizures following lithium pilocarpine (LiPc)-induced status epilepticus (SE) were treated with different doses of GBbf or vehicle for subsequent 4 weeks...
April 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28374506/g-csf-and-cognitive-dysfunction-in-elderly-diabetic-mice-with-cerebral-small-vessel-disease-preventive-intervention-effects-and-underlying-mechanisms
#9
Zhu-Fei Guan, Ying-Hong Tao, Xiao-Ming Zhang, Qi-Lin Guo, Ying-Chao Liu, Yu Zhang, Yan-Mei Wang, Gang Ji, Guo-Feng Wu, Na-Na Wang, Hao Yang, Zhong-Yu Yu, Jing-Chun Guo, Hou-Guang Zhou
AIMS: Although cognitive dysfunction is a common neurological complication in elderly patients with diabetes, the mechanisms underlying this relationship remain unclear, and effective preventive interventions have yet to be developed. Thus, this study investigated the preventive effects and mechanisms of action associated with granulocyte colony-stimulating factor (G-CSF) on cognitive dysfunction in elderly diabetic mice with cerebral small vessel disease. METHODS: This study included 40 male db/db diabetic and wild-type (WT) mice that were categorized into the following four groups at the age of 3 weeks: db/db group (DG), db/db+G-CSF group (DGG), WT group (WG), and WT+G-CSF group (WGG)...
April 4, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28373010/ecdysterones-from-rhaponticum-carthamoides-willd-iljin-reduce-hippocampal-excitotoxic-cell-loss-and-upregulate-mtor-signaling-in-rats
#10
Jiming Wu, Le Gao, Lei Shang, Guihua Wang, Nana Wei, Tiantian Chu, Suping Chen, Yujun Zhang, Jian Huang, Jinhui Wang, Ruichao Lin
Glutamate-induced excitotoxicity is a key pathological mechanism in many neurological disease states. Ecdysterones derived from Rhaponticum carthamoides (Willd.) Iljin (RCI) have been shown to alleviate glutamate-induced neuronal damage; although their mechanism of action is unclear, some data suggest that they enhance signaling in the mechanistic target of rapamycin (mTOR) signaling pathway. This study sought to elucidate the mechanisms underlying ecdysterone-mediated neuroprotection. We used in silico target prediction and simulation methods to identify putative ecdysterone binding targets, and to specifically identify those that represent nodes where several neurodegenerative diseases converge...
March 31, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28372486/the-effect-of-il-1%C3%AE-on-synaptophysin-expression-and-electrophysiology-of-hippocampal-neurons-through-the-pi3k-akt-mtor-signaling-pathway-in-a-rat-model-of-mesial-temporal-lobe-epilepsy
#11
Zhaohua Xiao, Jing Peng, Liwen Wu, Ahmed Arafat, Fei Yin
BACKGROUND: The inflammation induced by interleukin-1β (IL-1β) is a critical factor in the pathogenesis of mesial temporal lobe epilepsy (MTLE). Synaptophysin (SYN) and other changes, including neuron electrophysiology, participate in the pathophysiological processes of MTLE. Phosphatidylinositol 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) signaling pathway may play a critical role in regulating SYN expression and electrophysiology of hippocampal neurons. METHODS: We used lithium-pilocarpine-treated rats as model of human MTLE, detecting epileptic seizures with digital video-EEG, and evaluating the proteins related to the PI3K/Akt/mTOR signaling pathway by western blot (WB)...
April 4, 2017: Neurological Research
https://www.readbyqxmd.com/read/28366621/rescue-of-pink1-deficiency-by-stress-dependent-activation-of-autophagy
#12
Yuxi Zhang, David T Nguyen, Ellen M Olzomer, Gin P Poon, Nicholas J Cole, Anita Puvanendran, Brigitte R Phillips, Daniel Hesselson
Stimulating autophagy is a promising therapeutic strategy for slowing the progression of neurodegenerative disease. Neurons are insensitive to current approaches based on mTOR inhibition for activating autophagy, and instead may rely on the Parkinson's disease-associated proteins PINK1 and PARKIN to activate the autophagy-lysosomal pathway in response to mitochondrial damage. We developed a multifactorial zebrafish drug-screening platform combining Pink1 deficiency with an environmental toxin to compromise mitochondrial function and trigger dopaminergic neuron loss...
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28365975/neuroprotective-effect-of-duloxetine-on-chronic-cerebral-hypoperfusion-induced-hippocampal-neuronal-damage
#13
Jin-A Park, Choong-Hyun Lee
Chronic cerebral hypoperfusion (CCH), which is associated with onset of vascular dementia, causes cognitive impairment and neuropathological alterations in the brain. In the present study, we examined the neuroprotective effect of duloxetine (DXT), a potent and balanced serotonin/norepinephrine reuptake inhibitor, on CCH-induced neuronal damage in the hippocampal CA1 region using a rat model of permanent bilateral common carotid arteries occlusion. We found that treatment with 20 mg/kg DXT could attenuate the neuronal damage, the reduction of phosphorylations of mTOR and p70S6K as well as the elevations of TNF-α and IL- 1β levels in the hippocampal CA1 region at 28 days following CCH...
April 6, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28347403/lack-of-il-1r8-in-neurons-causes-hyperactivation-of-il-1-receptor-pathway-and-induces-mecp2-dependent-synaptic-defects
#14
Romana Tomasoni, Raffaella Morini, Jose P Lopez-Atalaya, Irene Corradini, Alice Canzi, Marco Rasile, Cristina Mantovani, Davide Pozzi, Cecilia Garlanda, Alberto Mantovani, Elisabetta Menna, Angel Barco, Michela Matteoli
Inflammation modifies risk and/or severity of a variety of brain diseases through still elusive molecular mechanisms. Here we show that hyperactivation of the interleukin 1 pathway, through either ablation of the interleukin 1 receptor 8 (IL-1R8, also known as SIGIRR or Tir8) or activation of IL-1R, leads to up-regulation of the mTOR pathway and increased levels of the epigenetic regulator MeCP2, bringing to disruption of dendritic spine morphology, synaptic plasticity and plasticity-related gene expression...
March 28, 2017: ELife
https://www.readbyqxmd.com/read/28346493/aberrant-neuronal-activity-induced-signaling-and-gene-expression-in-a-mouse-model-of-rasopathy
#15
Franziska Altmüller, Santosh Pothula, Anil Annamneedi, Saeideh Nakhaei-Rad, Carolina Montenegro-Venegas, Eneko Pina-Fernández, Claudia Marini, Monica Santos, Denny Schanze, Dirk Montag, Mohammad R Ahmadian, Oliver Stork, Martin Zenker, Anna Fejtova
Noonan syndrome (NS) is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the molecular mechanisms underlying cognitive impairments in NS patients are still poorly understood. Here, we report the generation and characterization of a new conditional mouse strain that expresses the overactive Ptpn11D61Y allele only in the forebrain...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28345605/extracellular-matrix-protein-reelin-promotes-myeloma-progression-by-facilitating-tumor-cell-proliferation-and-glycolysis
#16
Xiaodan Qin, Liang Lin, Li Cao, Xinwei Zhang, Xiao Song, Jie Hao, Yan Zhang, Risheng Wei, Xiaojun Huang, Jin Lu, Qing Ge
Reelin is an extracellular matrix protein that is crucial for neuron migration, adhesion, and positioning. We examined the expression of Reelin in a large cohort of multiple myeloma patients recorded in Gene Expression Omnibus (GEO) database and used over-expression and siRNA knockdown of Reelin to investigate the role of Reelin in myeloma cell growth. We find that Reelin expression is negatively associated with myeloma prognosis. Reelin promotes myeloma cell proliferation in vitro as well as in vivo. The Warburg effect, evidenced by increased glucose uptake and lactate production, is also enhanced in Reelin-expressing cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344003/abnormal-neural-progenitor-cells-differentiated-from-induced-pluripotent-stem-cells-partially-mimicked-development-of-tsc2-neurological-abnormalities
#17
Yaqin Li, Jiqing Cao, Menglong Chen, Jing Li, Yiming Sun, Yu Zhang, Yuling Zhu, Liang Wang, Cheng Zhang
Tuberous sclerosis complex (TSC) is a disease featuring devastating and therapeutically challenging neurological abnormalities. However, there is a lack of specific neural progenitor cell models for TSC. Here, the pathology of TSC was studied using primitive neural stem cells (pNSCs) from a patient presenting a c.1444-2A>C mutation in TSC2. We found that TSC2 pNSCs had higher proliferative activity and increased PAX6 expression compared with those of control pNSCs. Neurons differentiated from TSC2 pNSCs showed enlargement of the soma, perturbed neurite outgrowth, and abnormal connections among cells...
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28323869/tyrosine-mutated-aav2-mediated-shrna-silencing-of-pten-promotes-axon-regeneration-of-adult-optic-nerve
#18
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
#19
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
#20
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
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