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Pp2a memory cells

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https://www.readbyqxmd.com/read/27453502/prg-1-regulates-synaptic-plasticity-via-intracellular-pp2a-%C3%AE-1-integrin-signaling
#1
Xingfeng Liu, Jisen Huai, Heiko Endle, Leslie Schlüter, Wei Fan, Yunbo Li, Sebastian Richers, Hajime Yurugi, Krishnaraj Rajalingam, Haichao Ji, Hong Cheng, Benjamin Rister, Guilherme Horta, Jan Baumgart, Hendrik Berger, Gregor Laube, Ulrich Schmitt, Michael J Schmeisser, Tobias M Boeckers, Stefan Tenzer, Andreas Vlachos, Thomas Deller, Robert Nitsch, Johannes Vogt
Alterations in dendritic spine numbers are linked to deficits in learning and memory. While we previously revealed that postsynaptic plasticity-related gene 1 (PRG-1) controls lysophosphatidic acid (LPA) signaling at glutamatergic synapses via presynaptic LPA receptors, we now show that PRG-1 also affects spine density and synaptic plasticity in a cell-autonomous fashion via protein phosphatase 2A (PP2A)/β1-integrin activation. PRG-1 deficiency reduces spine numbers and β1-integrin activation, alters long-term potentiation (LTP), and impairs spatial memory...
August 8, 2016: Developmental Cell
https://www.readbyqxmd.com/read/26057947/systemic-pyruvate-administration-markedly-reduces-neuronal-death-and-cognitive-impairment-in-a-rat-model-of-alzheimer-s-disease
#2
Xiaonan Wang, Xuejun Hu, Yang Yang, Toshihiro Takata, Takashi Sakurai
Alzheimer's disease (AD) is a major neurodegenerative disease of old age, characterized by progressive cognitive impairment, dementia and atrophy of the central nervous system. Amyloid-β (Aβ) oligomers are derived from proteolytic cleavage of amyloid precursor protein (APP) and recognized as the primary neurotoxic agents in AD. Pyruvate has a protective effect against Aβ oligomer-induced neuronal cell death and inhibition of long-term potentiation (LTP) in hippocampal slice cultures, leading us to investigate the effect of systemic pyruvate administration in an intracerebroventricular Aβ oligomer infusion model...
September 2015: Experimental Neurology
https://www.readbyqxmd.com/read/25964356/regulation-of-ampa-receptor-phosphorylation-by-the-neuropeptide-pacap38
#3
Alyssa M A Toda, Richard L Huganir
Dynamic changes in synaptic strength are thought to be critical for higher brain function such as learning and memory. Alterations in synaptic strength can result from modulation of AMPA receptor (AMPAR) function and trafficking to synaptic sites. The phosphorylation state of AMPAR subunits is one mechanism by which cells regulate receptor function and trafficking. Receptor phosphorylation is in turn regulated by extracellular signals; these include neuronal activity, neuropeptides, and neuromodulators such as dopamine and norepinephrine (NE)...
May 26, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25737046/activation-of-the-5-amp-activated-protein-kinase-in-the-cerebral-cortex-of-young-senescence-accelerated-p8-mice-and-association-with-gsk3%C3%AE-and-pp2a-dependent-inhibition-of-p-tau%C3%A2-%C3%A2-%C3%A2-expression
#4
Hak-Su Kim, Sohee Moon, Jin-Hwe Paik, Dong Wun Shin, Lindsay S Kim, Chang-Shin Park, Joohun Ha, Ju-Hee Kang
The 5'-AMP-activated protein kinase (AMPK), which is a sensor of cellular energy, regulates neuronal survival and energy homeostasis. However, the roles of AMPK in the pathogenesis of Alzheimer's disease (AD) are unclear. The senescence-accelerated mouse prone 8 (SAMP8) strain is characterized by deficits in learning and memory, exhibits pathological characteristics of AD as early as 5 months of age, and is being increasingly recognized as a model of AD. Here, we investigated the relationship between AMPK activation and phosphorylation of the tau protein in the brain of young (2-month-old) SAMP8 animals and in differentiated SH-SY5Y cells...
2015: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/25589718/inhibition-of-protein-phosphatase-2a-pp2a-by-i1pp2a-leads-to-hyperphosphorylation-of-tau-neurodegeneration-and-cognitive-impairment-in-rats
#5
Xiaochuan Wang, Julie Blanchard, Yunn Chyn Tung, Inge Grundke-Iqbal, Khalid Iqbal
Protein phosphatase-2A (PP2A) deficiency is a cause of the abnormal hyperphosphorylation of tau, which composes neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brain. We previously reported that both mRNA and protein expression of inhibitor I of PP2A (I(1)(PP2A)) are elevated in AD brain and that this inhibitor induces a dose-dependent inhibition of PP2A activity and tau hyperphosphorylation in NIH3T3 cells. However, whether I(1)(PP2A) can induce AD neurofibrillary degeneration and cognitive impairment was not known...
2015: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/24987368/silencing-formula-see-text-rescues-tau-pathologies-and-memory-deficits-through-rescuing-pp2a-and-inhibiting-gsk-3%C3%AE-signaling-in-human-tau-transgenic-mice
#6
Yao Zhang, Rong-Hong Ma, Xia-Chun Li, Jia-Yu Zhang, Hai-Rong Shi, Wei Wei, Dan-Ju Luo, Qun Wang, Jian-Zhi Wang, Gong-Ping Liu
Increase of inhibitor-2 of protein phosphatase-2A [Formula: see text] is associated with protein phosphatase-2A (PP2A) inhibition and tau hyperphosphorylation in Alzheimer's disease (AD). Down-regulating [Formula: see text] attenuated amyloidogenesis and improved the cognitive functions in transgenic mice expressing amyloid precursor protein (tg2576). Here, we found that silencing [Formula: see text] by hippocampal infusion of [Formula: see text] down-regulated [Formula: see text] (~45%) with reduction of tau phosphorylation/accumulation, improvement of memory deficits, and dendritic plasticity in 12-month-old human tau transgenic mice...
2014: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/24885237/intermittent-hypoxia-induced-protein-phosphatase-2a-activation-reduces-pc12-cell-proliferation-and-differentiation
#7
Tsung-I Chen, Hung-Wen Chiu, Yi-Chung Pan, Shih-Ting Hsu, Jian-Hong Lin, Kun-Ta Yang
BACKGROUND: Intermittent hypoxia (IH) plays a critical role in sleep breathing disorder-associated hippocampus impairments, including neurocognitive deficits, irreversible memory and learning impairments. IH-induced neuronal injury in the hippocampus may result from reduced precursor cell proliferation and the relative numbers of postmitotic differentiated neurons. However, the mechanisms underlying IH-induced reactive oxygen species (ROS) generation effects on cell proliferation and neuronal differentiation remain largely unknown...
May 16, 2014: Journal of Biomedical Science
https://www.readbyqxmd.com/read/24707311/new-treatment-for-alzheimer-s-disease-kamikihito-reverses-amyloid-%C3%AE-induced-progression-of-tau-phosphorylation-and-axonal-atrophy
#8
Hidetoshi Watari, Yutaka Shimada, Chihiro Tohda
Aims. We previously reported that kamikihito (KKT), a traditional Japanese medicine, improved memory impairment and reversed the degeneration of axons in the 5XFAD mouse model of Alzheimer's disease (AD). However, the mechanism underlying the effects of KKT remained unknown. The aim of the present study was to investigate the mechanism by which KKT reverses the progression of axonal degeneration. Methods. Primary cultured cortical neurons were treated with amyloid beta (A β ) fragment comprising amino acid residues (25-35) (10  μ M) in an in vitro AD model...
2014: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/24523662/contribution-of-orb2a-stability-in-regulated-amyloid-like-oligomerization-of-drosophila-orb2
#9
Erica White-Grindley, Liying Li, Repon Mohammad Khan, Fengzhen Ren, Anita Saraf, Laurence Florens, Kausik Si
How learned experiences persist as memory for a long time is an important question. In Drosophila the persistence of memory is dependent upon amyloid-like oligomers of the Orb2 protein. However, it is not clear how the conversion of Orb2 to the amyloid-like oligomeric state is regulated. The Orb2 has two protein isoforms, and the rare Orb2A isoform is critical for oligomerization of the ubiquitous Orb2B isoform. Here, we report the discovery of a protein network comprised of protein phosphatase 2A (PP2A), Transducer of Erb-B2 (Tob), and Lim Kinase (LimK) that controls the abundance of Orb2A...
February 2014: PLoS Biology
https://www.readbyqxmd.com/read/23922015/silencing-pp2a-inhibitor-by-lenti-shrna-interference-ameliorates-neuropathologies-and-memory-deficits-in-tg2576-mice
#10
Gong-Ping Liu, Wei Wei, Xin Zhou, Hai-Rong Shi, Xing-Hua Liu, Gao-Shang Chai, Xiu-Qing Yao, Jia-Yu Zhang, Cai-Xia Peng, Juan Hu, Xia-Chun Li, Qun Wang, Jian-Zhi Wang
Deficits of protein phosphatase-2A (PP2A) play a crucial role in tau hyperphosphorylation, amyloid overproduction, and synaptic suppression of Alzheimer's disease (AD), in which PP2A is inactivated by the endogenously increased inhibitory protein, namely inhibitor-2 of PP2A (I2(PP2A)). Therefore, in vivo silencing I2(PP2A) may rescue PP2A and mitigate AD neurodegeneration. By infusion of lentivirus-shRNA targeting I2(PP2A) (LV-siI2(PP2A)) into hippocampus and frontal cortex of 11-month-old tg2576 mice, we demonstrated that expression of LV-siI2(PP2A) decreased remarkably the elevated I2(PP2A) in both mRNA and protein levels...
December 2013: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/23763493/pp2a-ligand-ith12246-protects-against-memory-impairment-and-focal-cerebral-ischemia-in-mice
#11
Silvia Lorrio, Alejandro Romero, Laura González-Lafuente, Rocío Lajarín-Cuesta, Francisco J Martínez-Sanz, Martín Estrada, Abdelouahid Samadi, Jose Marco-Contelles, María Isabel Rodríguez-Franco, Mercedes Villarroya, Manuela G López, Cristóbal de los Ríos
ITH12246 (ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate) is a 1,8-naphthyridine described to feature an interesting neuroprotective profile in in vitro models of Alzheimer's disease. These effects were proposed to be due in part to a regulatory action on protein phosphatase 2A inhibition, as it prevented binding of its inhibitor okadaic acid. We decided to investigate the pharmacological properties of ITH12246, evaluating its ability to counteract the memory impairment evoked by scopolamine, a muscarinic antagonist described to promote memory loss, as well as to reduce the infarct volume in mice suffering phototrombosis...
September 18, 2013: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/23415654/molecular-and-cellular-effects-of-vitamin-b12-in-brain-myocardium-and-liver-through-its-role-as-co-factor-of-methionine-synthase
#12
REVIEW
Jean-Louis Guéant, Maatem Caillerez-Fofou, Shyuefang Battaglia-Hsu, Jean-Marc Alberto, Jean-Noel Freund, Isabelle Dulluc, Charles Adjalla, Florence Maury, Carole Merle, Jean-Pierre Nicolas, Fares Namour, Jean-Luc Daval
Vitamin B12 (cobalamin, cbl) is a cofactor of methionine synthase (MTR) in the synthesis of methionine, the precursor of the universal methyl donor S-Adenosylmethionine (SAM), which is involved in epigenomic regulatory mechanisms. We have established a neuronal cell model with stable expression of a transcobalamin-oleosin chimer and subsequent decreased cellular availability of vitamin B12, which produces reduced proliferation, increased apoptosis and accelerated differentiation through PP2A, NGF and TACE pathways...
May 2013: Biochimie
https://www.readbyqxmd.com/read/22976297/a-key-phosphorylation-site-in-ac8-mediates-regulation-of-ca-2-dependent-camp-dynamics-by-an-ac8-akap79-pka-signalling-complex
#13
Debbie Willoughby, Michelle L Halls, Katy L Everett, Antonio Ciruela, Philipp Skroblin, Enno Klussmann, Dermot M F Cooper
Adenylyl cyclase (AC) isoforms can participate in multimolecular signalling complexes incorporating A-kinase anchoring proteins (AKAPs). We recently identified a direct interaction between Ca(2+)-sensitive AC8 and plasma membrane-targeted AKAP79/150 (in cultured pancreatic insulin-secreting cells and hippocampal neurons), which attenuated the stimulation of AC8 by Ca(2+) entry (Willoughby et al., 2010). Here, we reveal that AKAP79 recruits cAMP-dependent protein kinase (PKA) to mediate the regulatory effects of AKAP79 on AC8 activity...
December 1, 2012: Journal of Cell Science
https://www.readbyqxmd.com/read/22914323/pp2a-dependent-control-of-transcriptionally-active-foxo3a-in-cd8-central-memory-lymphocyte-survival-requires-p47-phox
#14
Q Liu, L Yi, S Sadiq-Ali, S M Koontz, A Wood, N Zhu, S H Jackson
Forkhead box O3a (FOXO3a) transcription factor is regulated by complex post-translational modifications that allow for transcriptional control of various apoptosis factors including pro-apoptotic Bim. Although it has been shown that kinases phosphorylate FOXO3a in memory T cells, the role of protein phosphatases in the control of memory T lymphocyte FOXO3a function is less clear. Here, we report that FOXO3a is dephosphorylated (activated) by a protein phosphatase 2A (PP2A)-dependent mechanism in CD8(+) memory lymphocytes (Tm) during Listeria monocytogenes (Lm) infection, which allows for enhanced Bim transcription in nicotinamide adenine dinucleotide phosphate-oxidase p47(phox)-deficient (p47(phox-/-)) Tm...
August 23, 2012: Cell Death & Disease
https://www.readbyqxmd.com/read/22748295/different-designs-of-kinase-phosphatase-interactions-and-phosphatase-sequestration-shapes-the-robustness-and-signal-flow-in-the-mapk-cascade
#15
Uddipan Sarma, Indira Ghosh
BACKGROUND: The three layer mitogen activated protein kinase (MAPK) signaling cascade exhibits different designs of interactions between its kinases and phosphatases. While the sequential interactions between the three kinases of the cascade are tightly preserved, the phosphatases of the cascade, such as MKP3 and PP2A, exhibit relatively diverse interactions with their substrate kinases. Additionally, the kinases of the MAPK cascade can also sequester their phosphatases. Thus, each topologically distinct interaction design of kinases and phosphatases could exhibit unique signal processing characteristics, and the presence of phosphatase sequestration may lead to further fine tuning of the propagated signal...
July 2, 2012: BMC Systems Biology
https://www.readbyqxmd.com/read/22451307/pyruvate-prevents-the-inhibition-of-the-long-term-potentiation-induced-by-amyloid-%C3%AE-through-protein-phosphatase-2a-inactivation
#16
Xiaonan Wang, Toshihiro Takata, Xiaojuan Bai, Fengrong Ou, Koichi Yokono, Takashi Sakurai
Amyloid-β (Aβ) oligomers are derived from proteolytic cleavage of amyloid-β protein precursor and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. Pyruvate has a protective effect against Aβ-induced neuronal cell death in hippocampal slice cultures. However, whether pyruvate also has a protective effect against the inhibition of neuronal plasticity induced by Aβ remains to be elucidated. This study examined the effect of pyruvate on the Aβ-induced inhibition of LTP in the rat hippocampus...
2012: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/21046238/lead-dysregulates-serine-threonine-protein-phosphatases-in-human-neurons
#17
Abdur Rahman, Bruce J Brew, Gilles J Guillemin
It is well established that lead (Pb) exposure in humans leads to learning and memory impairment. However, the biological and molecular mechanisms are still not clearly understood. When over activated, serine/threonine protein phosphatases are known to function as a constraint on learning and memory. Activation of these phosphatases can also result in cytoskeletal changes that will adversely affect learning and memory. We investigated the effects of Pb exposure on these phosphatases in primary cultures of human neurons...
February 2011: Neurochemical Research
https://www.readbyqxmd.com/read/20651003/the-carboxy-terminal-fragment-of-inhibitor-2-of-protein-phosphatase-2a-induces-alzheimer-disease-pathology-and-cognitive-impairment
#18
Xiaochuan Wang, Julie Blanchard, Erik Kohlbrenner, Nathalie Clement, R Michael Linden, Aurelian Radu, Inge Grundke-Iqbal, Khalid Iqbal
Development of rational therapeutic treatments of Alzheimer disease (AD) requires the elucidation of the etiopathogenic mechanisms of neurofibrillary degeneration and β-amyloidosis, the two hallmarks of this disease. Here we show, employing an adeno-associated virus serotype 1 (AAV1)-induced expression of the C-terminal fragment (I(2CTF)) of I(2)(PP2A), also called SET, in rat brain, decrease in protein phosphatase 2A (PP2A) activity, abnormal hyperphosphorylation of tau, and neurodegeneration; littermates treated identically but with vector only, i...
November 2010: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/20643941/sodium-selenate-mitigates-tau-pathology-neurodegeneration-and-functional-deficits-in-alzheimer-s-disease-models
#19
Janet van Eersel, Yazi D Ke, Xin Liu, Fabien Delerue, Jillian J Kril, Jürgen Götz, Lars M Ittner
Alzheimer's disease (AD) brains are characterized by amyloid-beta-containing plaques and hyperphosphorylated tau-containing neurofibrillary tangles (NFTs); however, in frontotemporal dementia, the tau pathology manifests in the absence of overt amyloid-beta plaques. Therapeutic strategies so far have primarily been targeting amyloid-beta, although those targeting tau are only slowly beginning to emerge. Here, we identify sodium selenate as a compound that reduces tau phosphorylation both in vitro and in vivo...
August 3, 2010: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/20537899/sodium-selenate-specifically-activates-pp2a-phosphatase-dephosphorylates-tau-and-reverses-memory-deficits-in-an-alzheimer-s-disease-model
#20
Niall M Corcoran, Daniel Martin, Birgit Hutter-Paier, Manfred Windisch, Thanh Nguyen, Lina Nheu, Lars E Sundstrom, Anthony J Costello, Christopher M Hovens
Neurofibrillary tangles composed of abnormally hyperphosphorylated tau protein are a hallmark of Alzheimer's disease (AD) and related tauopathies. Tau hyperphosphorylation is thought to promote aggregation with subsequent tangle formation. Reducing tau phosphorylation by boosting the activity of the key phosphatase/s that mediate dephosphorylation of tau could be a viable clinical strategy in AD. One of the key phosphatases implicated in regulating tau protein phosphorylation is the serine-threonine phosphatase PP2A...
August 2010: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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