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mTOR in neuron

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https://www.readbyqxmd.com/read/28520507/gold-nanoparticles-enhance-the-differentiation-of-embryonic-stem-cells-into-dopaminergic-neurons-via-mtor-p70s6k-pathway
#1
Min Wei, Song Li, Zhaofei Yang, Wei Zheng, Weidong Le
AIM: This study aimed to investigate the effect of gold nanoparticles (AuNPs) on differentiation of mouse embryonic stem cells (ESCs) into dopaminergic (DA) neurons and explore the possible underlying molecular mechanisms. MATERIALS & METHODS: The efficiency of AuNPs on DA neuron differentiation was evaluated by observing fluorescence in TH promoter-engineered GFP-reporter ESCs, western blot and real-time PCR. The possible signal pathway was determined by western blot...
May 18, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28515679/downregulation-of-the-repressor-element-1-silencing-transcription-factor-rest-is-associated-with-akt-mtor-and-wnt-%C3%AE-catenin-signaling-in-prion-diseases-models
#2
Zhiqi Song, Syed Z A Shah, Wei Yang, Haodi Dong, Lifeng Yang, Xiangmei Zhou, Deming Zhao
Prion diseases are a group of infectious diseases characterized by multiple neuropathological changes, yet the mechanisms that preserve function and protect against prion-associated neurodegeneration are still unclear. We previously reported that the repressor element 1-silencing transcription factor (REST) alleviates neurotoxic prion peptide (PrP106-126)-induced toxicity in primary neurons. Here we confirmed the findings of the in vitro model in 263K infected hamsters, an in vivo model of prion diseases and further showed the relationships between REST and related signaling pathways...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28507979/microtubule-associated-protein-tau-is-associated-with-the-resistance-to-docetaxel-in-prostate-cancer-cell-lines
#3
Jian Yang, Yang Yu, Wei Liu, Zhi Li, Zhongqing Wei, Rongjiang Jiang
Tau, a microtubule-associated protein, has been investigated primarily in neurons. Recently, tau has been explored to be associated with increased drug resistance in various kinds of cancers. We found that the tau was expressed in prostate cancer cell lines DU145 and PC-3. We also reported that recurrent prostate cancer cells after docetaxel treatment have higher levels of microtubule-associated protein tau. In vitro, inactivation of tau by gene knockdown suppressed cell proliferation and sensitized docetaxel cytotoxicity...
2017: Research and Reports in Urology
https://www.readbyqxmd.com/read/28504198/rapamycin-suppresses-a%C3%AE-25-35-or-lps-induced-neuronal-inflammation-via-modulation-of-nf-%C3%AE%C2%BAb-signaling
#4
Ying-Chun Liu, Xiao-Xiao Gao, Ling Chen, Xiao-Qing You
Rapamycin (RAPA), an inhibitor of mammalian target of rapamycin (mTOR), exhibits a high neuroprotective action against neurodegenerative diseases in mouse models. Since neuroinflammation has been shown to be involved in Alzheimer's disease (AD) development and progression, the aim of this study was to examine the anti-inflammatory role of RAPA in AD in vivo and in vitro, and investigate the underlying mechanisms. We found that amyloid-β (Aβ) induced neuronal inflammation and a remarkable increase in mTOR activity in in-vivo and in-vitro models of inflammation, suggesting the critical role of mTOR signaling in neuronal inflammation...
May 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28501494/focused-microwave-irradiation-assisted-immunohistochemistry-to-study-effects-of-ketamine-on-phospho-erk-expression-in-the-mouse-brain
#5
Alda Fernandes, Yu-Wen Li
Ketamine produces rapid and long-lasting antidepressant effects in depressive patients. Preclinical studies demonstrate that ketamine stimulates AMPA receptor transmission and activates BDNF/TrkB-Akt/ERK-mTOR signaling cascades, leading to a sustained increase in synaptic protein synthesis and strengthening of synaptic plasticity, a potential mechanism underlying the antidepressant effects. The purpose of this study was to develop an immunohistochemistry (IHC) assay to map the distribution of extracellular signal-regulated kinase (ERK) phosphorylation in the mouse brain in response to systemic ketamine treatment...
May 10, 2017: Brain Research
https://www.readbyqxmd.com/read/28499802/ampk-activates-foxo3a-and-promotes-neuronal-apoptosis-in-the-developing-rat-brain-during-the-early-phase-after-hypoxia-ischemia
#6
Deyuan Li, Lili Luo, Min Xu, Jinlin Wu, Lina Chen, Jinhui Li, Zhongqiang Liu, Guoyan Lu, Yang Wang, Lina Qiao
AMP-activated protein kinase (AMPK) is a key metabolic and stress sensor/effector. Few investigations have been performed to study the role of AMPK in developing rat brain with hypoxia-ischemia (HI). Forkhead transcriptional factor (FOXO3a) has been revealed to be a critical effector of AMPK-mediated celluar apoptosis. However, it is not clear whether AMPK/FOXO3a pathway is involved in neuronal apoptosis in the developing rat brain after HI. In this study, we generated hypoxia-ischemia brain damage (HIBD) model using postnatal day 7 rats...
May 10, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28494938/pi3k-akt-mtor-signaling-mediates-valproic-acid-induced-neuronal-differentiation-of-neural-stem-cells-through-epigenetic-modifications
#7
Xi Zhang, Xiaosong He, Qingqing Li, Xuejian Kong, Zhenri Ou, Le Zhang, Zhuo Gong, Dahong Long, Jianhua Li, Meng Zhang, Weidong Ji, Wenjuan Zhang, Liping Xu, Aiguo Xuan
Although valproic acid (VPA), has been shown to induce neuronal differentiation of neural stem cells (NSCs), the underlying mechanisms remain poorly understood. Here we investigated if and how mammalian target of rapamycin (mTOR) signaling is involved in the neuronal differentiation of VPA-induced NSCs. Our data demonstrated that mTOR activation not only promoted but also was necessary for the neuronal differentiation of NSCs induced by VPA. We further found that inhibition of mTOR signaling blocked demethylation of neuron-specific gene neurogenin 1 (Ngn1) regulatory element in induced cells...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28489581/high-glucose-induces-formation-of-tau-hyperphosphorylation-via-cav-1-mtor-pathway-a-potential-molecular-mechanism-for-diabetes-induced-cognitive-dysfunction
#8
Jing Wu, Shan-Lei Zhou, Lin-Hua Pi, Xia-Jie Shi, Ling-Ran Ma, Zi Chen, Min-Li Qu, Xin Li, Sheng-Dan Nie, Duan-Fang Liao, Jin-Jing Pei, Shan Wang
The abnormally hyperphosphorylated tau is thought to be implicated in diabetes-associated cognitive deficits. The role of mammalian target of rapamycin (mTOR) / S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation has been previously studied. Caveolin-1 (Cav-1), the essential structure protein of caveolae, promotes neuronal survival and growth, and inhibits glucose metabolism. In this study, we aimed to investigate the role of Cav-1 in the formation of tau hyperphosphorylation under chronic hyperglycemic condition (HGC)...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28484273/role-of-akt-independent-mtorc1-and-gsk3%C3%AE-signaling-in-sublethal-nmda-induced-injury-and-the-recovery-of-neuronal-electrophysiology-and-survival
#9
Przemyslaw Swiatkowski, Ina Nikolaeva, Gaurav Kumar, Avery Zucco, Barbara F Akum, Mihir V Patel, Gabriella D'Arcangelo, Bonnie L Firestein
Glutamate-induced excitotoxicity, mediated by overstimulation of N-methyl-D-aspartate (NMDA) receptors, is a mechanism that causes secondary damage to neurons. The early phase of injury causes loss of dendritic spines and changes to synaptic activity. The phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt/ mammalian target of rapamycin (PI3K/Akt/mTOR) pathway has been implicated in the modulation and regulation of synaptic strength, activity, maturation, and axonal regeneration. The present study focuses on the physiology and survival of neurons following manipulation of Akt and several downstream targets, such as GSK3β, FOXO1, and mTORC1, prior to NMDA-induced injury...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28472467/hypothalamic-regulation-of-liver-and-muscle-nutrient-partitioning-by-brain-specific-carnitine-palmitoyltransferase-1c-cpt1c-in-male-mice
#10
Macarena Pozo, Rosalía Rodríguez-Rodríguez, Sara Ramírez, Patricia Seoane-Collazo, Miguel López, Dolors Serra, Laura Herrero, Núria Casals
Carnitine palmitoyltransferase 1C (CPT1C), a brain-specific protein localized in the endoplasmic reticulum of neurons, is expressed in almost all brain regions. Based on global knockout (KO) models, CPT1C has demonstrated relevance in hippocampus-dependent spatial learning as well as in hypothalamic regulation of energy balance. Specifically, it has been shown that CPT1C is protective against high-fat diet-induced obesity (DIO), and that CPT1C KO mice show reduced peripheral fatty acid oxidation (FAO) both during fasting and DIO...
May 3, 2017: Endocrinology
https://www.readbyqxmd.com/read/28469644/the-emerging-role-of-autophagic-lysosomal-dysfunction-in-gaucher-disease-and-parkinson-s-disease
#11
REVIEW
Kerri J Kinghorn, Amir M Asghari, Jorge Iván Castillo-Quan
Gaucher disease (GD), the commonest lysosomal storage disorder, results from the lack or functional deficiency of glucocerebrosidase (GCase) secondary to mutations in the GBA1 gene. There is an established association between GBA1 mutations and Parkinson's disease (PD), and indeed GBA1 mutations are now considered to be the greatest genetic risk factor for PD. Impaired lysosomal-autophagic degradation of cellular proteins, including α-synuclein (α-syn), is implicated in the pathogenesis of PD, and there is increasing evidence for this also in GD and GBA1-PD...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28469639/telomerase-and-mtor-in-the-brain-the-mitochondria-connection
#12
REVIEW
Satomi Miwa, Gabriele Saretzki
Telomerase is an enzyme that maintains telomeres in dividing cells using a template on its inherent RNA component. Additionally, the protein part TERT (Telomerase Reverse Transcriptase) has various non-canonical functions. For example, it can localize to mitochondria under increased stress and protect cells in vitro from oxidative stress, DNA damage and apoptosis. Recently it has been demonstrated that TERT protein persists in adult neurons in the brain and data emerge suggesting that it might have a protective function in these post-mitotic cells as well...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28466267/17%C3%AE-estradiol-via-sirt1-acetyl-p53-nf-kb-signaling-pathway-rescued-postnatal-rat-brain-against-acute-ethanol-intoxication
#13
Mehtab Khan, Shahid Ali Shah, Myeong Ok Kim
Growing evidences reveal that 17β-estradiol has a wide variety of neuroprotective potential. Recently, it has been shown that 17β-estradiol can limit ethanol-induced neurotoxicity in neonatal rats. Whether it can stimulate SIRT1 signaling against ethanol intoxicity in developing brain remain elusive. Here, we report for the first time that 17β-estradiol activated SIRT1 to deacetylate p53 proteins against acute ethanol-induced oxidative stress, neuroinflammation, and neurodegeneration. A single subcutaneous injection of ethanol-induced oxidative stress triggered phospho c-jun N terminal kinase (p-JNK) and phospho mammalian target of rapamycin (p-mTOR) accompanied by neuroinflammation and widespread neurodegeneration...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28457820/differential-roles-for-akt-and-mtorc1-in-the-hypertrophy-of-pten-mutant-neurons-a-cellular-model-of-brain-overgrowth-disorders
#14
Ina Nikolaeva, Tatiana M Kazdoba, Beth Crowell, Gabriella D'Arcangelo
Mutations in the PI3K/Akt/mTOR signaling pathway or in the upstream negative regulator Pten cause human brain overgrowth disorders, such as focal cortical dysplasia and megalencephaly, and are characterized by the presence of hypertrophic neurons. These disorders often have a pediatric onset and a high comorbidity with drug-resistant epilepsy; however, effective pharmacological treatments are lacking. We established forebrain excitatory neuron-specific Pten-deficient cultures as an in vitro model of brain overgrowth disorders, and investigated the effects of this Pten mutation on PI3K/Akt/mTOR signaling and neuronal growth...
April 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/28456145/autophagy-plays-beneficial-effect-on-diabetic-encephalopathy-in-type-2-diabetes-studies-in-vivo-and-in-vitro
#15
Yu-Hong Jing, Lang Zhang, Li-Ping Gao, Chu-Chu Qi, Dan-Dan Lv, Yan-Feng Song, Jie Yin, De-Gui Wang
OBJECTIVES: The hypothalamus regulates metabolism and feeding behavior by perceiving the levels of peripheral insulin. However, little is known about the hypothalamic changes after aberrant metabolism. In this study, we investigated the changes of insulin and autophagy relevant signals of hypothalamus under diabetes mellitus. METHODS: C57B/L mice were injected with low-dose streptozotocin (STZ) and fed with high-fat diet to induce type 2 diabetes mellitus. In vitro, PC12 cells were treated with oleic acid to mimic lipotoxicity...
February 15, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28434145/mtorc1-signaling-in-hepatic-lipid-metabolism
#16
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
#17
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
#18
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...
May 2, 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
#19
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
#20
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
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