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https://www.readbyqxmd.com/read/28809765/cyclin-dependent-kinase-5-modulates-the-p2x2a-receptor-channel-gating-through-phosphorylation-of-c-terminal-threonine-372
#1
Claudio Coddou, Rodrigo Sandoval, Patricio Castro, Pablo Lazcano, Maria José Hevia, Milos Rokic, Bradford Hall, Anita Terse, Christian Gonzalez-Billault, Ashok B Kulkarni, Stanko S Stojilkovic, Elias Utreras
The purinergic P2X2 receptor (P2X2R) is an adenosine triphosphate-gated ion channel widely expressed in the nervous system. Here, we identified a putative cyclin-dependent kinase 5 (Cdk5) phosphorylation site in the full-size variant P2X2aR (TPKH), which is absent in the splice variant P2X2bR. We therefore investigated the effects of Cdk5 and its neuronal activator, p35, on P2X2aR function. We found an interaction between P2X2aR and Cdk5/p35 by co-immunofluorescence and co-immunoprecipitation in HEK293 cells...
July 17, 2017: Pain
https://www.readbyqxmd.com/read/28782589/the-role-of-thioredoxin-1-in-resisting-methamphetamine-induced-rewarding-effect
#2
Mengbing Huang, Lingpin Kong, Lihua Yang, Xiang Li, Xiaoshuang Zhou, Ye Li, Jie Bai
Methamphetamine (METH) is a highly addictive drug of abuse which induces behavioral sensitization and rewarding effects. Thioredoxin-1 (Trx-1) is a redox protein and plays role in regulating activity of transcription factor, such as cAMP responsive element-binding protein (CREB), AP-1, p53, is emerging as an important modulator of neuronal function. It has been reported that Trx-1 is involved in morphine dependence. In this study, we examined the rewarding effect after METH administration by conditioned place preference (CPP) of mice, and detected the levels of dopamine and the activity of cAMP responsive element-binding protein (CREB), the expressions of ΔFosB and cyclin-dependent kinase 5 (CDK5) in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in mice...
August 4, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28765091/lead-exposure-and-tau-hyperphosphorylation-an-in-vitro-study
#3
Syed Waseem Bihaqi, Aseel Eid, Nasser H Zawia
The presence of fibrillary lesions, which are mainly composed of the microtubule associated protein tau (MAPT) in neurons, has gained immense recognition due to their presence in numerous neurodegenerative diseases, including Alzheimer's disease (AD). Dysregulation of tau is related with its altered site-specific phosphorylation which is followed by tau polymerization, neuronal dysfunction and death. Previous reports by us suggest that molecular alterations favor abundant tau phosphorylation and immunoreactivity in the frontal cortex of aged primates and rodents with past exposure to lead (Pb)...
July 29, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28760951/cdk5-dependent-phosphorylation-of-liprin%C3%AE-1-mediates-neuronal-activity-dependent-synapse-development
#4
Huiqian Huang, Xiaochen Lin, Zhuoyi Liang, Teng Zhao, Shengwang Du, Michael M T Loy, Kwok-On Lai, Amy K Y Fu, Nancy Y Ip
The experience-dependent modulation of brain circuitry depends on dynamic changes in synaptic connections that are guided by neuronal activity. In particular, postsynaptic maturation requires changes in dendritic spine morphology, the targeting of postsynaptic proteins, and the insertion of synaptic neurotransmitter receptors. Thus, it is critical to understand how neuronal activity controls postsynaptic maturation. Here we report that the scaffold protein liprinα1 and its phosphorylation by cyclin-dependent kinase 5 (Cdk5) are critical for the maturation of excitatory synapses through regulation of the synaptic localization of the major postsynaptic organizer postsynaptic density (PSD)-95...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28754891/cyclin-dependent-kinase-5-novel-role-of-gene-variants-identified-in-adhd
#5
Subhamita Maitra, Mahasweta Chatterjee, Swagata Sinha, Kanchan Mukhopadhyay
Cortical neuronal migration and formation of filamentous actin cytoskeleton, needed for development, normal cell growth and differentiation, are regulated by the cyclin-dependent kinase 5 (Cdk5). Attention deficit hyperactivity disorder (ADHD) is associated with delayed maturation of the brain and hence we hypothesized that cdk5 may have a role in ADHD. Eight functional CDK5 gene variants were analyzed in 848 Indo-Caucasoid individuals including 217 families with ADHD probands and 250 healthy volunteers. Only three variants, rs2069454, rs2069456 and rs2069459, predicted to affect transcription, were found to be bimorphic...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28751497/cdk5-mcl-1-axis-promotes-mitochondrial-dysfunction-and-neurodegeneration-in-alzheimer-s-disease-model
#6
Kumar Nikhil, Kavita Shah
Cdk5 deregulation is highly neurotoxic in AD. We identified Mcl-1 as a direct Cdk5 substrate using an innovative chemical screen in mouse brain lysates. Our data demonstrate that Mcl-1 levels determine the threshold for cellular damage in response to neurotoxic insults. Mcl-1 is a disease-specific target of Cdk5, which associates with Cdk5 under basal conditions, however, is not regulated by it. Neurotoxic insults hyperactivate Cdk5 causing Mcl-1 phosphorylation at T92. This phosphorylation event triggers Mcl-1 ubiquitylation, which directly correlates with mitochondrial dysfunction...
July 27, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28733456/nestin-contributes-to-skeletal-muscle-homeostasis-and-regeneration
#7
Julia Lindqvist, Elin Torvaldson, Josef Gullmets, Henok Karvonen, Andras Nagy, Pekka Taimen, John E Eriksson
Nestin, a member of the cytoskeletal family of intermediate filaments, regulates the onset of myogenic differentiation through bidirectional signaling with the Cdk5-kinase. Here we show that these effects are also reflected at the organism level, as there is a loss of skeletal muscle mass in nestin(-/-) (NesKO) mice, reflected as reduced lean mass in the mice. Further examination of muscles in male mice revealed that these effects stemmed from nestin-deficient muscles being more prone to spontaneous regeneration...
July 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28729771/microarray-gene-expression-analysis-of-chemosensitivity-for-docetaxel-cisplatin-and-5-fluorouracil-tpf-combined-chemotherapeutic-regimen-in-hypopharyngeal-squamous-cell-carcinoma
#8
Meng Lian, Haizhou Wang, Jugao Fang, Jie Zhai, Ru Wang, Xixi Shen, Yifan Yang, Zhihong Ma, Honggang Liu
OBJECTIVE: To screen out a set of candidate genes which could help to determine whether patients with hypopharyngeal squamous cell carcinoma (HSCC) could benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy. METHODS: Gene-expression profiles in 12 TPF-sensitive patients were compared to 9 resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line FaDu after TPF treatment were observed by quantitative real-time polymerase chain reaction (qRT-PCR)...
June 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28720653/three-dimensional-structural-analysis-reveals-a-cdk5-mediated-kinase-cascade-regulating-hepatic-biliary-network-branching-in-zebrafish
#9
Manali Dimri, Cassandra Bilogan, Lain X Pierce, Gregory Naegele, Amit Vasanji, Isabel Gibson, Allyson McClendon, Kevin Tae, Takuya F Sakaguchi
The intrahepatic biliary network is a highly branched three-dimensional network lined by biliary epithelial cells, but how its branching patterns are precisely established is not clear. We designed a new computer-based algorithm that quantitatively computes the structural differences of the three-dimensional networks. Utilizing the algorithm, we showed that inhibition of Cyclin-dependent kinase 5 (Cdk5) led to reduced branching in the intrahepatic biliary network in zebrafish. Further, we identified a previously unappreciated downstream kinase cascade regulated by Cdk5...
July 15, 2017: Development
https://www.readbyqxmd.com/read/28717189/cdk5-mediated-phosphorylation-of-xbp1s-contributes-to-its-nuclear-translocation-and-activation-in-mpp-induced-parkinson-s-disease-model
#10
Feng-Juan Jiao, Qing-Zhi Wang, Pei Zhang, Jian-Guo Yan, Zheng Zhang, Feng He, Qian Zhang, Ze-Xi Lv, Xiang Peng, Hong-Wei Cai, Bo Tian
Parkinson's disease (PD) is an irreversible and progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta. Growing evidence indicates that endoplasmic reticulum stress is a hallmark of PD; however, its exact contribution to the disease process remains poorly understood. Here, we used molecular biology methods and RNA-Seq analysis to explored an unexpected role of spliced X-Box binding protein 1 (XBP1s) in the nervous system. In this study, we determined that the IRE1α/XBP1 pathway is activated in MPP(+)-treated neurons...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714390/cdk5-and-mapt-gene-expression-in-alzheimer-s-disease-brain-samples
#11
Josianne Thomazini Fukasawa, Roger Willian de Labio, Lucas Trevizani Rasmussen, Lucieni Conterno de Oliveira, Elizabeth Chen, João Villares, Gustavo Tureck, Marília de Arruda Cardoso Smith, Spencer Luiz Marques Payão
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid plaque and neurofibrillary tangles in the brain. Studies have shown that neurons are able to re-enter the cell cycle, but not enough to enable full replication. This leads to cell death and consequent neurodegeneration. OBJECTIVE: This study aimed to characterize the expression of the MAPT gene and CDK5 (the gene involved in cell cycle regulation) in brain samples from patients with AD and controls...
July 13, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28694424/a-tricyclic-antidepressant-amoxapine-reduces-amyloid-%C3%AE-generation-through-multiple-serotonin-receptor-6-mediated-targets
#12
Xiaohang Li, Qinying Wang, Tingting Hu, Ying Wang, Jian Zhao, Jing Lu, Gang Pei
Alzheimer's disease (AD) is a major and devastating neurodegenerative disease, and the amyloid-β (Aβ) hypothesis is still the central theory for AD pathogenesis. Meanwhile, another major mental illness, depression, is one of the risk factors for AD. From a high-throughput screening (HTS), amoxapine, a typical secondary amine tricyclic antidepressant (TCA), was identified to reduce Aβ production. A follow-up investigation on antidepressants showed that most of the TCAs harbour similar activity. Previous studies have indicated that TCAs improve cognitive function in AD mouse models as well as in preliminary clinical data; however, the underlying mechanism is controversial, and the effect on Aβ is elusive...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28674940/characterization-of-the-cdk5-gene-in-apis-cerana-cerana-acccdk5-and-a-preliminary-identification-of-its-activator-gene-acccdk5r1
#13
Guangdong Zhao, Chen Wang, Hongfang Wang, Lijun Gao, Zhenguo Liu, Baohua Xu, Xingqi Guo
Cyclin-dependent kinase 5 (CDK5) is an unusual CDK whose function has been implicated in protecting the central nervous system (CNS) from oxidative damage. However, there have been few studies of CDK5 in insects. In this study, we identified the AccCDK5 gene from Apis cerana cerana and investigated its role in oxidation resistance. We found that AccCDK5 is highly conserved across species and contains conserved features of the CDK5 family. The results of qPCR analysis indicated that AccCDK5 is highly expressed during the larval and pupal stages and in the adult head and muscle...
July 3, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28670853/the-pathological-roles-of-ndrg2-in-alzheimer-s-disease-a-study-using-animal-models-and-appwt-overexpressed-cells
#14
Xian-Fang Rong, Ying-Ni Sun, Dong-Mei Liu, Hua-Jing Yin, Ying Peng, Shao-Feng Xu, Ling Wang, Xiao-Liang Wang
AIMS: To investigate the roles of N-myc downstream-regulated gene 2 (NDRG2) in the pathology of aging and neurodegenerative disease such as Alzheimer's disease (AD). RESULTS: In this study, we confirmed the upregulation of NDRG2 in the brains of aging and AD animal models. To explore the role of NDRG2 in the pathology of AD at molecular level, we conducted a cell-based assay of highly expressed wild-type human APP695 SK-N-SH cells (SK-N-SH APPwt). By silencing and overexpressing gene of NDRG2, we demonstrated that NDRG2-mediated increase in Aβ1-42 was through the pathways of BACE1 and GGA3...
July 2, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28660485/crmp2-phosphorylation-drives-glioblastoma-cell-proliferation
#15
Aubin Moutal, Lex Salas Villa, Seul Ki Yeon, Kyle T Householder, Ki Duk Park, Rachael W Sirianni, Rajesh Khanna
Glioblastoma (GBM) is an aggressive primary brain tumor. The rapid growth and the privileged provenance of the tumor within the brain contribute to its aggressivity and poor therapeutic targeting. A poor prognostic factor in glioblastoma is the deletion or mutation of the Nf1 gene. This gene codes for the protein neurofibromin, a tumor suppressor gene that is known to interact with the collapsin response mediator protein 2 (CRMP2). CRMP2 expression and elevated expression of nuclear phosphorylated CRMP2 have recently been implicated in cancer progression...
June 28, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28648896/inhibition-of-cdk5-alleviates-the-cardiac-phenotypes-in-timothy-syndrome
#16
LouJin Song, Seon-Hye E Park, Yehuda Isseroff, Kumi Morikawa, Masayuki Yazawa
L-type calcium channel CaV1.2 plays an essential role in cardiac function. The gain-of-function mutations in CaV1.2 have been reported to be associated with Timothy syndrome, a disease characterized by QT prolongation and syndactyly. Previously we demonstrated that roscovitine, a cyclin-dependent kinase (CDK) inhibitor, could rescue the phenotypes in induced pluripotent stem cell-derived cardiomyocytes from Timothy syndrome patients. However, exactly how roscovitine rescued the phenotypes remained unclear. Here we report a mechanism potentially underlying the therapeutic effects of roscovitine on Timothy syndrome cardiomyocytes...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28646794/dexibuprofen-prevents-neurodegeneration-and-cognitive-decline-in-appswe-ps1de9-through-multiple-signaling-pathways
#17
Miren Ettcheto, Elena Sánchez-López, Laura Pons, Oriol Busquets, Jordi Olloquequi, Carlos Beas-Zarate, Merce Pallas, Maria Luisa García, Carme Auladell, Jaume Folch, Antoni Camins
The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28641077/inhibition-of-early-growth-response-1-in-the-hippocampus-alleviates-neuropathology-and-improves-cognition-in-an-alzheimer-model-with-plaques-and-tangles
#18
Xike Qin, Yunling Wang, Hemant K Paudel
A sporadic form of Alzheimer disease (AD) and vascular dementia share many risk factors, and their pathogenic mechanisms are suggested to be related. Transcription factor early growth response 1 (Egr-1) regulates various vascular pathologies and is up-regulated in both AD brains and AD mouse models; however, its role in AD pathogenesis is unclear. Herein, we report that silencing of Egr-1 in the hippocampus by shRNA reduces tau phosphorylation, amyloid-β (Aβ) pathology, and improves cognition in the 3xTg-AD mouse model...
June 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28640256/microrna-26a-cyclin-dependent-kinase-5-axis-controls-proliferation-apoptosis-and-in-vivo-tumor-growth-of-diffuse-large-b-cell-lymphoma-cell-lines
#19
Floriana Maria Farina, Alessandra Inguscio, Paolo Kunderfranco, Alice Cortesi, Leonardo Elia, Manuela Quintavalle
Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. Despite a favorable therapeutic response to first-line chemo-immunotherapy, still 30-40% of patients is refractory, or relapse after this treatment. Thus, alternative strategies must be sought. Previous studies have indicated that cyclin-dependent kinase 5 (CDK5), a serine/threonine protein kinase, is involved in tumor development and progression, and it may represent a potential therapeutic target. However, its role in modulating DLBCL growth and progression remains largely unexplored...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28639593/synaptic-roles-of-cyclin-dependent-kinase-5-its-implications-in-epilepsy
#20
REVIEW
Aparna Banerjee Dixit, Jyotirmoy Banerjee, Manjari Tripathi, Chitra Sarkar, P Sarat Chandra
There is an urgent need to understand the molecular mechanisms underlying epilepsy to find novel prognostic/diagnostic biomarkers to prevent epilepsy patients at risk. Cyclin-dependent kinase 5 (CDK5) is involved in multiple neuronal functions and plays a crucial role in maintaining homeostatic synaptic plasticity by regulating intracellular signalling cascades at synapses. CDK5 deregulation is shown to be associated with various neurodegenerative diseases such as Alzheimer's disease. The association between chronic loss of CDK5 and seizures has been reported in animal models of epilepsy...
February 2017: Indian Journal of Medical Research
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