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https://www.readbyqxmd.com/read/28215400/somatic-mutations-in-tsc1-and-tsc2-cause-focal-cortical-dysplasia
#1
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...
February 12, 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
#2
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
#3
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
#4
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.
February 10, 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
#5
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
#6
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
#7
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)...
February 9, 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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28135561/focal-cortical-dysplasia-gene-mutations-cell-signaling-and-therapeutic-implications
#13
Philip H Iffland, Peter B Crino
Focal cortical dysplasias (FCDs) are malformations of cortical development (MCDs) that are highly associated with medication-resistant epilepsy and are the most common cause of neocortical epilepsy in children. FCDs are a heterogeneous group of developmental disorders caused by germline or somatic mutations that occur in genes regulating the PI3K/Akt/mTOR pathway-a key pathway in neuronal growth and migration. Accordingly, FCDs are characterized by abnormal cortical lamination, cell morphology (e.g., cytomegaly), and cellular polarity...
January 24, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/28134789/mrpl10-and-tbp-are-suitable-reference-genes-for-peripheral-nerve-crush-injury
#14
Yaxian Wang, Qianqian Shan, Yali Meng, Jiacheng Pan, Sheng Yi
Peripheral nerve injury triggers the dysregulation of a large number of genes at multiple sites, including neurons, peripheral nerve stump, and the target organ. Housekeeping genes were frequently used as reference genes to normalize the expression values of target genes. Suitable selection of housekeeping genes that are stably expressed after nerve injury minimizes bias elicited by reference genes and thus helps to better and more sensitively reflect gene expression changes. However, many housekeeping genes have been used as reference genes without testing the expression patterns of themselves...
January 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28131834/7-4-hydroxy-3-methoxyphenyl-1-phenyl-4e-hepten-3-one-alleviates-a%C3%AE-1-42-induced-cytotoxicity-through-pi3k-mtor-pathways
#15
Hanlin Xiao, Qinghua Zhang, Yinghui Peng, Genyun Tang, Yumei Liao, Xiaoji Zhuang, Wen-Cai Ye, Ying Wang, Lei Shi
Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly. Increasing evidence has shown that β-amyloid protein (Aβ) production is the key pathological cause of AD. 7-(4-Hydroxy-3-methoxyphenyl)-1-phenyl-4E-hepten-3-one (AO-2), a natural diarylheptanoid, is previously found to have activities in neuronal differentiation and neurite outgrowth, and its analogue shows protective effects against Aβ. In this study, we further investigated the function of AO-2 toward Aβ-induced injuries in PC12 cells and hippocampal neurons...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28131727/long-term-protective-effects-of-aav9-mesencephalic-astrocyte-derived-neurotrophic-factor-gene-transfer-in-parkinsonian-rats
#16
Fei Hao, Chun Yang, Sha-Sha Chen, Yan-Yan Wang, Wei Zhou, Qiang Hao, Tao Lu, Barry Hoffer, Li-Ru Zhao, Wei-Ming Duan, Qun-Yuan Xu
Intrastriatal injection of mesencephalic astrocyte-derived neurotrophic factor (MANF) protein has been shown to provide neuroprotective and neurorestorative effects in a 6-hydroxydopamine (6-OHDA) - lesioned rat model of Parkinson's disease. Here, we used an adeno-associated virus serotype 9 (AAV9) vector to deliver the human MANF (hMANF) gene into the rat striatum 10days after a 6-OHDA lesion to examine long-term effects of hMANF on nigral dopaminergic neurons and mechanisms underlying MANF neuroprotection...
January 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28131206/pik3ca-mutation-in-a-mixed-dysembryoplastic-neuroepithelial-tumor-and-rosette-forming-glioneuronal-tumor-a-case-report-and-literature-review
#17
Philip George Eye, Laurence Davidson, Patrick J Malafronte, Sarah Cantrell, Brett J Theeler
BACKGROUND: Rosette forming glioneuronal tumors are rare, World Health Organization (WHO) grade I novel tumors frequently affecting the fourth ventricle or posterior fossa with typical neuronal pseudorosettes. RGNTs have been described as possessing additional histologic features of DNETs or pilocytic astrocytomas. Activating PIK3CA mutations have been identified as recurring genetic event in RGNTs. METHODS: We report a 35year old man who presented with binocular diplopia, headache, and was found to have a third ventricle tumor...
February 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28130174/exercise-increases-mtor-signaling-in-brain-regions-involved-in-cognition-and-emotional-behavior
#18
Brian A Lloyd, Holly S Hake, Takayuki Ishiwata, Caroline E Farmer, Esteban C Loetz, Monika Fleshner, Sondra T Bland, Benjamin N Greenwood
Exercise can enhance learning and memory and produce resistance against stress-related psychiatric disorders such as depression and anxiety. In rats, these beneficial effects of exercise occur regardless of exercise controllability: both voluntary and forced wheel running produce stress-protective effects. The mechanisms underlying these beneficial effects of exercise remain unknown. The mammalian target of rapamycin (mTOR) is a translation regulator important for cell growth, proliferation, and survival. mTOR has been implicated in enhancing learning and memory as well as antidepressant effects...
January 24, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28121223/using-tuberous-sclerosis-complex-to-understand-the-impact-of-mtorc1-signaling-on-mitochondrial-dynamics-and-mitophagy-in-neurons
#19
Darius Ebrahimi-Fakhari, Afshin Saffari, Lara Wahlster, Mustafa Sahin
Constitutive activation of the MTOR pathway is a key feature of defects in the tuberous sclerosis complex and other genetic neurodevelopmental diseases, collectively referred to as MTORopathies. MTORC1 hyperactivity promotes anabolic cell functions such as protein synthesis, yet at the same time catabolic processes such as macroautophagy/autophagy are suppressed. Mitochondria are major substrates of autophagy; however, their role in MTORopathies remains largely undefined. Here, we review our recent study showing that several aspects of mitochondrial function, dynamics and turnover are critically impaired in neuronal models of TSC...
January 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28119058/analysis-of-ribosomal-protein-s6-baseline-phosphorylation-and-effect-of-tau-pathology-in-the-murine-brain-and-human-hippocampus
#20
Maria Klingebiel, Maja Dinekov, Christoph Köhler
We examined the distribution pattern of the phosphorylated 40S ribosomal subunit protein S6, a downstream target of the mTOR pathway, in the brains of 24-months-old human tau transgenic pR5 mice, non-transgenic littermates and in human hippocampi. We studied baseline levels of phosphorylated S6 and a possible effect of tau pathology. S6 phosphorylated at Ser235/236 (pS6Ser235/236) or Ser240/244 (pS6Ser240/244) has been used as a read-out of mTOR activity in several studies. The mTOR pathway regulates a wide variety of cellular functions including cell growth, ribosome biosynthesis, translational control and autophagy...
January 21, 2017: Brain Research
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