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GSK3 AND Aging

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https://www.readbyqxmd.com/read/28808220/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#1
Xunxian Liu, Zemin Yao
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28638339/nutritional-and-pharmacological-strategies-to-regulate-microglial-polarization-in-cognitive-aging-and-alzheimer-s-disease
#2
REVIEW
Emiliano Peña-Altamira, Sabrina Petralla, Francesca Massenzio, Marco Virgili, Maria L Bolognesi, Barbara Monti
The study of microglia, the immune cells of the brain, has experienced a renaissance after the discovery of microglia polarization. In fact, the concept that activated microglia can shift into the M1 pro-inflammatory or M2 neuroprotective phenotypes, depending on brain microenvironment, has completely changed the understanding of microglia in brain aging and neurodegenerative diseases. Microglia polarization is particularly important in aging since an increased inflammatory status of body compartments, including the brain, has been reported in elderly people...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#3
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28440874/role-of-glycogen-synthase-kinase-3-in-ischemia-induced-blood-brain-barrier-disruption-in-aged-female-rats
#4
Han Xiao, Mingyang Deng, Binbin Yang, Jianguang Tang, Zhiping Hu
Estrogen receptors have protective effects against ischemic brain injury. However, the molecular mechanisms underlying this phenomenon have yet to be well studied. Given that inhibition of glycogen synthase kinase (GSK3) can reduce cerebral ischemia/reperfusion injury, we hypothesized that estrogen receptors-mediated protective effects against ischemia-induced blood-brain barrier (BBB) disruption involve inhibition of GSK3. Thus, we evaluated GSK3 expression in the brain of ovariectomized female rats, and examined the effects of intracerebroventricular pre-treatments of SB216763, GSK3 inhibitor, on BBB permeability following middle cerebral artery occlusion (MCAO)...
July 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28281664/genetic-interactions-and-functional-analyses-of-the-fission-yeast-gsk3-and-amk2-single-and-double-mutants-defective-in-torc1-dependent-processes
#5
Charalampos Rallis, StJohn Townsend, Jürg Bähler
The Target of Rapamycin (TOR) signalling network plays important roles in aging and disease. The AMP-activated protein kinase (AMPK) and the Gsk3 kinase inhibit TOR during stress. We performed genetic interaction screens using synthetic genetic arrays (SGA) with gsk3 and amk2 as query mutants, the latter encoding the regulatory subunit of AMPK. We identified 69 negative and 82 positive common genetic interactors, with functions related to cellular growth and stress. The 120 gsk3-specific negative interactors included genes functioning in translation and ribosomes...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28238722/hormetic-modulation-of-hepatic-insulin-sensitivity-by-advanced-glycation-end-products
#6
Nelly T Fabre, Karina Thieme, Karolline S Silva, Sérgio Catanozi, Ana Mercedes Cavaleiro, Danilo A C Pinto, Maristela M Okamoto, Mychel Raony P T Morais, Bárbara Falquetto, Telma M Zorn, Ubiratan F Machado, Marisa Passarelli, Maria Lúcia Correa-Giannella
Because of the paucity of information regarding metabolic effects of advanced glycation end products (AGEs) on liver, we evaluated effects of AGEs chronic administration in (1) insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation and; (3) hepatic morphology and glycogen content. Rats received intraperitoneally albumin modified (AlbAGE) or not by advanced glycation for 12 weeks. AlbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes...
February 24, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28110316/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#7
X Liu, Z Yao
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27875990/inverse-relationship-between-alzheimer-s-disease-and-cancer-and-other-factors-contributing-to-alzheimer-s-disease-a-systematic-review
#8
REVIEW
Ovais Shafi
BACKGROUND: The AD etiology is yet not properly known. Interactions among environmental factors, multiple susceptibility genes and aging, contribute to AD. This study investigates the factors that play role in causing AD and how changes in cellular pathways contribute to AD. METHODS: PUBMED database, MEDLINE database and Google Scholar were searched with no date restrictions for published articles involving cellular pathways with roles in cancers, cell survival, growth, proliferation, development, aging, and also contributing to Alzheimer's disease...
November 22, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27783302/perinatal-brain-injury-is-accompanied-by-disturbances-in-expression-of-slc-protein-superfamily-in-endotheliocytes-of-hippocampal-microvessels
#9
A V Morgun, N V Kuvacheva, E D Khilazheva, E A Pozhilenkova, Ya V Gorina, N A Malinovskaya, Yu K Komleva, O L Lopatina, Yu A Panina, E D Gasymly, A B Salmina
The peculiarities in expression of transport proteins and the proteins implicated in the control of glycolysis by the cellular components of neurovascular units were examined in animals of different age under normal conditions and after modeled perinatal stress or hypoxic brain injury. In both cases, the specialties in expression of transport proteins in ontogenesis were revealed. The perinatal hypoxic brain injury resulted in up-regulation of MCT1, MCT4, and GLUT4 expression in endotheliocytes of hippocampal microvessels accompanied by transient elevation of HIF-1α and GSK3 expression...
October 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27493677/chronic-over-nutrition-and-dysregulation-of-gsk3-in-diseases
#10
REVIEW
Xunxian Liu, Zemin Yao
Loss of cellular response to hormonal regulation in maintaining metabolic homeostasis is common in the process of aging. Chronic over-nutrition may render cells insensitive to such a hormonal regulation owing to overstimulation of certain signaling pathways, thus accelerating aging and causing diseases. The glycogen synthase kinase 3 (GSK3) plays a pivotal role in relaying various extracellular and intracellular regulatory signals critical to cell growth, survival, regeneration, or death. The main signaling pathway regulating GSK3 activity through serine-phosphorylation is the phosphoinositide 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/Akt relay that catalyzes serine-phosphorylation and thus inactivation of GSK3...
2016: Nutrition & Metabolism
https://www.readbyqxmd.com/read/27485139/neuroprotective-effect-of-ginsenoside-rg1-prevents-cognitive-impairment-induced-by-isoflurane-anesthesia-in-aged-rats-via-antioxidant-anti-inflammatory-and-anti-apoptotic-effects-mediated-by-the-pi3k-akt-gsk-3%C3%AE-pathway
#11
Yini Zhang, Zhao Zhang, Haitang Wang, Nan Cai, Shuang Zhou, Yaoping Zhao, Xue Chen, Shaoqiang Zheng, Qi Si, Wei Zhang
Ginsenoside Rg1 is the primary active substance in ginseng, and it has multiple pharmacological actions. Investigations on the pharmacologic action of ginsenoside Rg1 have developed, with a particular focus on the regulation of metabolism. The present study hypothesized that the neuroprotective effects of ginsenoside Rg1 prevent cognitive impairment induced by isoflurane anesthesia via antioxidant, anti‑inflammatory and anti‑apoptotic effects, mediated by the phosphoinositide 3‑kinase (PI3K)/AKT/glycogen synthase kinase‑3β (GSK‑3β) pathway in aged rats...
September 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27353310/gsk3%C3%AE-hyperactivity-during-an-early-critical-period-impairs-prefrontal-synaptic-plasticity-and-induces-lasting-deficits-in-spine-morphology-and-working-memory
#12
Bo Xing, Yan-Chun Li, Wen-Jun Gao
Schizophrenia (SZ) is a neurodevelopmental disorder in which the emergence of cognitive symptoms occurs during early adolescence. Glycogen synthase kinase-3β (GSK3β) plays a critical role in synaptic plasticity during development and is highly implicated in the etiology of SZ. However, how GSK3β activity affects synaptic plasticity and working memory function in the prefrontal cortex (PFC) during development remains unknown. Here we show a GSK3β hyperactivity during the early postnatal period in a neurodevelopmental rat SZ model that receives gestational exposure (E17) to the neurotoxin methylazoxymethanol (MAM)...
December 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27312991/cholinergic-surveillance-over-hippocampal-rna-metabolism-and-alzheimer-s-like-pathology
#13
Benjamin Kolisnyk, Mohammed Al-Onaizi, Lilach Soreq, Shahar Barbash, Uriya Bekenstein, Nejc Haberman, Geula Hanin, Maxine T Kish, Jussemara Souza da Silva, Margaret Fahnestock, Jernej Ule, Hermona Soreq, Vania F Prado, Marco A M Prado
The relationship between long-term cholinergic dysfunction and risk of developing dementia is poorly understood. Here we used mice with deletion of the vesicular acetylcholine transporter (VAChT) in the forebrain to model cholinergic abnormalities observed in dementia. Whole-genome RNA sequencing of hippocampal samples revealed that cholinergic failure causes changes in RNA metabolism. Remarkably, key transcripts related to Alzheimer's disease are affected. BACE1, for instance, shows abnormal splicing caused by decreased expression of the splicing regulator hnRNPA2/B1...
July 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/27068460/lithium-promotes-longevity-through-gsk3-nrf2-dependent-hormesis
#14
Jorge Iván Castillo-Quan, Li Li, Kerri J Kinghorn, Dobril K Ivanov, Luke S Tain, Cathy Slack, Fiona Kerr, Tobias Nespital, Janet Thornton, John Hardy, Ivana Bjedov, Linda Partridge
The quest to extend healthspan via pharmacological means is becoming increasingly urgent, both from a health and economic perspective. Here we show that lithium, a drug approved for human use, promotes longevity and healthspan. We demonstrate that lithium extends lifespan in female and male Drosophila, when administered throughout adulthood or only later in life. The life-extending mechanism involves the inhibition of glycogen synthase kinase-3 (GSK-3) and activation of the transcription factor nuclear factor erythroid 2-related factor (NRF-2)...
April 19, 2016: Cell Reports
https://www.readbyqxmd.com/read/27028000/mitogenic-signaling-pathways-in-the-liver-of-growth-hormone-gh-overexpressing-mice-during-the-growth-period
#15
Carolina S Martinez, Verónica G Piazza, Lorena González, Yimin Fang, Andrzej Bartke, Danie Turynl, Johanna G Miquet, Ana I Sotelo
Growth hormone (GH) is a pleiotropic hormone that triggers STATs, ERK1/2 and Akt signaling, related to cell growth and proliferation. Transgenic mice overexpressing GH present increased body size, with a disproportionate liver enlargement due to hypertrophy and hyperplasia of the hepatocytes. We had described enhanced mitogenic signaling in liver of young adult transgenic mice. We now evaluate the activation of these signaling cascades during the growth period and relate them to the morphological alterations found...
2016: Cell Cycle
https://www.readbyqxmd.com/read/26991739/selective-tuberous-sclerosis-complex-1-gene-deletion-in-smooth-muscle-activates-mammalian-target-of-rapamycin-signaling-and-induces-pulmonary-hypertension
#16
Amal Houssaini, Shariq Abid, Geneviève Derumeaux, Feng Wan, Aurélien Parpaleix, Dominique Rideau, Elisabeth Marcos, Kanny Kebe, Gabor Czibik, Daigo Sawaki, Caroline Treins, Jean-Luc Dubois-Randé, Zhenlin Li, Valérie Amsellem, Larissa Lipskaia, Mario Pende, Serge Adnot
Constitutive activation of the mammalian target of rapamycin (mTOR) complexes mTORC1 and mTORC2 is associated with pulmonary hypertension (PH) and sustained growth of pulmonary artery (PA) smooth muscle cells (SMCs). We investigated whether selective mTORC1 activation in SMCs induced by deleting the negative mTORC1 regulator tuberous sclerosis complex 1 gene (TSC1) was sufficient to produce PH in mice. Mice expressing Cre recombinase under SM22 promoter control were crossed with TSC1(LoxP/LoxP) mice to generate SM22-TSC1(-/-) mice...
September 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/26971897/gsk3%C3%A3-dependent-dysregulation-of-neurodevelopment-in-spg11-patient-ipsc-model
#17
Himanshu K Mishra, Iryna Prots, Steven Havlicek, Zacharias Kohl, Francesc Perez-Branguli, Tom Boerstler, Lukas Anneser, Georgia Minakaki, Holger Wend, Martin Hampl, Marina Leone, Martina Brückner, Jochen Klucken, Andre Reis, Leah Boyer, Gerhard Schuierer, Jürgen Behrens, Angelika Lampert, Felix B Engel, Fred H Gage, Jürgen Winkler, Beate Winner
OBJECTIVE: Mutations in the Spastic Paraplegia Gene11 (SPG11), encoding spatacsin, cause the most frequent form of autosomal recessive (AR) complex hereditary spastic paraplegia (HSP) and juvenile onset amyotrophic lateral sclerosis (ALS5). When SPG11 is mutated, patients frequently present with spastic paraparesis, a thin corpus callosum, and cognitive impairment. We previously delineated a neurodegenerative phenotype in neurons of these patients. In the current study, we recapitulated early developmental phenotypes of SPG11 and outlined their cellular and molecular mechanisms in patient-specific induced pluripotent stem cell (iPSC) derived cortical neural progenitor cells (NPCs)...
March 11, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/26786352/decreased-adiponectin-links-elevated-adipose-tissue-autophagy-with-adipocyte-endocrine-dysfunction-in-obesity
#18
N Slutsky, M Vatarescu, Y Haim, N Goldstein, B Kirshtein, I Harman-Boehm, Y Gepner, I Shai, N Bashan, M Blüher, A Rudich
BACKGROUND/OBJECTIVES: Adipose tissue (AT) autophagy gene expression is elevated in human obesity, correlating with increased metabolic risk, but mechanistic links between the two remain unclear. Thus, the objective of this study was to assess whether elevated autophagy may cause AT endocrine dysfunction, emphasizing the putative role of adiponectin in fat-liver endocrine communication. SUBJECTS/METHODS: We utilized a large (N=186) human AT biobank to assess clinical associations between human visceral AT autophagy genes, adiponectin and leptin, by multivariate models...
June 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/26527066/enhanced-fgf23-production-in-mice-expressing-pi3k-insensitive-gsk3-is-normalized-by-%C3%AE-blocker-treatment
#19
Abul Fajol, Hong Chen, Anja T Umbach, L Darryl Quarles, Florian Lang, Michael Föller
Glycogen synthase kinase (GSK)-3 is a ubiquitously expressed kinase inhibited by insulin-dependent Akt/PKB/SGK. Mice expressing Akt/PKB/SGK-resistant GSK3α/GSK3β (gsk3(KI)) exhibit enhanced sympathetic nervous activity and phosphaturia with decreased bone density. Hormones participating in phosphate homeostasis include fibroblast growth factor (FGF)-23, a bone-derived hormone that inhibits 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) formation and phosphate reabsorption in the kidney and counteracts vascular calcification and aging...
February 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/26497034/brain-insulin-administration-triggers-distinct-cognitive-and-neurotrophic-responses-in-young-and-aged-rats
#20
Clarissa B Haas, Eduardo Kalinine, Eduardo R Zimmer, Gisele Hansel, Andressa W Brochier, Jean P Oses, Luis V Portela, Alexandre P Muller
Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24 months) and young (4 months) male Wistar rats were intracerebroventricularly injected with insulin (20 mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze...
November 2016: Molecular Neurobiology
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