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Pp2a memory cells

Dandan Yan, Jianling Yao, Ying Liu, Xing Zhang, Yiqi Wang, Xiaoyi Chen, Liegang Liu, Nian Shi, Hong Yan
Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin...
April 26, 2018: Brain, Behavior, and Immunity
Ghada A Abdel-Aleem, Eman F Khaleel
This study aimed at studying the potential neuroprotective effect of Rutin hydrate (RH) alone or in conjugation with α-tocopherol against cadmium chloride (CdCl2 )-induced neurotoxicity and cognitive impairment in rats and to investigate the mechanisms of action. Rats intoxicated with CdCl2 were treated with the vehicle, RH, α-tocopherol or combined treatment were examined, and compared to control rats received vehicle or individual doses of either drug. Data confirmed that RH improves spatial memory function by increasing acetylcholine availability, boosting endogenous antioxidant potential, activating cell survival and inhibiting apoptotic pathways, an effect that is more effective when RH was conjugated with α-tocopherol...
December 7, 2017: Archives of Physiology and Biochemistry
Muna L Hilal, Maité M Moreau, Claudia Racca, Vera L Pinheiro, Nicolas H Piguel, Marie-Josée Santoni, Steve Dos Santos Carvalho, Jean-Michel Blanc, Yah-Se K Abada, Ronan Peyroutou, Chantal Medina, Hélène Doat, Thomas Papouin, Laurent Vuillard, Jean-Paul Borg, Rivka Rachel, Aude Panatier, Mireille Montcouquiol, Stéphane H R Oliet, Nathalie Sans
Planar cell polarity (PCP) signaling is well known to play a critical role during prenatal brain development; whether it plays specific roles at postnatal stages remains rather unknown. Here, we investigated the role of a key PCP-associated gene scrib in CA1 hippocampal structure and function at postnatal stages. We found that Scrib is required for learning and memory consolidation in the Morris water maze as well as synaptic maturation and NMDAR-dependent bidirectional plasticity. Furthermore, we unveiled a direct molecular interaction between Scrib and PP1/PP2A phosphatases whose levels were decreased in postsynaptic density of conditional knock-out mice...
December 1, 2017: Cerebral Cortex
Sarada Subramanian, Ganesh Savanur, Sowmya Madhavadas
Alzheimer's disease (AD) is the leading cause of dementia, characterized by progressive loss of memory and other cognitive functions. The cognitive impairment in patients with AD is closely associated with loss of synapses and the formation of neurofibrillary tangles (NFT) containing hyperphosphorylated tau in the hippocampus. Effective treatment for AD is still not available. In this study, the sequence comprising of residues 50-71 in the N-terminal region of tau, containing theoretically predicted B- and T-cell epitopes in close proximity to pathologically relevant phospho-serine (residue 68) and phospho-threonine (residues 69, 71) was selected as a potential immunotherapeutic peptide...
January 29, 2017: Biochemical and Biophysical Research Communications
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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