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https://www.readbyqxmd.com/read/29158185/cdk5-mediated-phosphorylation-of-sirt2-contributes-to-depressive-like-behavior-induced-by-social-defeat-stress
#1
Zheng Zhang, Pei Zhang, Guang-Jian Qi, Feng-Juan Jiao, Qing-Zhi Wang, Jian-Guo Yan, Feng He, Qian Zhang, Ze-Xi Lv, Xiang Peng, Hong-Wei Cai, Xiaoqian Chen, Ning Sun, Bo Tian
Major depressive disorder (MDD) is a common, severe and recurrent psychiatric disorder worldwide; however, the underlying neuropathological mechanisms remain elusive. Histone deacetylases (HDACs) appear to play an essential role in depression. As the class III HDACs, Sirt1 and Sirt2 have attracted the most interest in the nervous system. Indeed, chronic stress decreased Sirt1 activity and down-regulated Sirt1 gene expression in MDD. Nevertheless, there is a paucity of literature on the role of Sirt2. To study the role of Sirt2 we established a MDD mouse model in wild type and Sirt2 knockout C57BL/6 mice using social defeat stress (SDS)...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29154274/cognitive-decline-in-preclinical-alzheimer-s-disease-amyloid-beta-versus-tauopathy
#2
Colin M Huber, Connor Yee, Taylor May, Apoorva Dhanala, Cassie S Mitchell
 We perform a large-scale meta-analysis of 51 peer-reviewed 3xTg-AD mouse publications to compare Alzheimer's disease (AD) quantitative clinical outcome measures, including amyloid-β (Aβ), total tau, and phosphorylated tau (pTau), with cognitive performance in Morris water maze (MWM) and Novel Object Recognition (NOR). "High" levels of Aβ (Aβ40, Aβ42) showed significant but weak trends with cognitive decline (MWM: slope = 0.336, R2 = 0.149, n = 259, p < 0.001; NOR: slope = 0.156, R2 = 0...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29152905/the-gait-translational-control-system
#3
REVIEW
Abul Arif, Peng Yao, Fulvia Terenzi, Jie Jia, Partho Sarothi Ray, Paul L Fox
The interferon (IFN)-γ-activated inhibitor of translation (GAIT) system directs transcript-selective translational control of functionally related genes. In myeloid cells, IFN-γ induces formation of a multiprotein GAIT complex that binds structural GAIT elements in the 3'-untranslated regions (UTRs) of multiple inflammation-related mRNAs, including ceruloplasmin and VEGF-A, and represses their translation. The human GAIT complex is a heterotetramer containing glutamyl-prolyl tRNA synthetase (EPRS), NS1-associated protein 1 (NSAP1), ribosomal protein L13a (L13a), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)...
November 20, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29150675/mechanisms-by-which-in-vitro-meiotic-arrest-and-sexual-maturity-improve-developmental-potential-of-mouse-oocytes
#4
Fei Chen, Juan Lin, Xue Sun, Bin Xiao, Shu-Fen Ning, Shuai Zhu, Hui-Li Wang, Jing-He Tan
To study the relationship between chromatin condensation, gene transcription and developmental competence during oocyte maturation and to explore the mechanisms by which meiotic arrest maintenance (MAM) and sexual maturity improve oocyte competence, we examined effects of MAM with roscovitine or db-cAMP on chromatin condensation, gene transcription and developmental potential of NSN or SN oocytes from prepubertal or adult mice. MAM with roscovitine improved the developmental competence and global gene transcription of prepubertal NSN (prep-NSN) and adult-SN oocytes while having no effect on those of prep-SN oocytes...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141245/roscovitine-a-cdk5-inhibitor-alleviates-sevoflurane-induced-cognitive-dysfunction-via-regulation-tau-gsk3%C3%AE-and-erk-ppar%C3%AE-creb-signaling
#5
Jianhui Liu, Junjun Yang, Yinhua Xu, Gang Guo, Li Cai, Heng Wu, Yanhong Zhao, Xiaoqing Zhang
BACKGROUND/AIMS: Multiple exposures to anesthesia in children may increase the risk of developing cognitive impairment. Sevoflurane is an anesthetic that is commonly used in children during surgery. Cyclin-dependent kinase (CDK) 5 is involved in the regulation of sevoflurane-induced cognitive dysfunction, but the mechanistic details remain unclear. The present study evaluated the mechanism by which CDK5 mediates sevoflurane-induced cognitive dysfunction in mice. METHODS: Hippocampal neurons were isolated from postnatal day 0 C57BL/6 mouse pups...
November 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29132690/cyclin-dependent-kinase-5-regulates-mapk-erk-signaling-in-the-skin-of-mice
#6
Xuexian Liu, Pengqian Zhang, Kaiyuan Ji, Junzhen Zhang, Shanshan Yang, Bin Du, Shuaipeng Hu, Ruiwen Fan
Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine/threonine kinase that has been shown to play important roles in many tissues except the nervous system. We previously reported that CDK5 showed differential expression in the transcriptome profiles of the skin of alpacas with different hair colors. To understand the functional role of CDK5 in hair color determination, we constructed CDK5-knockdown mice and identified the effect on the mitogen-activated protein kinase (MAPK) pathway in the mouse skin...
November 11, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29128902/overexpression-of-5-lipoxygenase-worsens-the-phenotype-of-a-mouse-model-of-tauopathy
#7
Phillip F Giannopoulos, Domenico Praticò
Brain accumulation of increasing amount of phosphorylated microtubule associated tau protein is one the major hallmark lesions of Alzheimer's disease (AD) and related tauopathies. Consistent evidence from clinical and animal studies has shown that neuroinflammation characterizes these diseases. The 5-lipoxygenase (5LO) is an enzyme protein whose metabolic products are lipids with potent inflammatory actions. Previously, we showed that blockade of 5LO activation ameliorates the phenotype of the htau transgenic mice...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29111393/cyclin-dependent-kinase-5-mediated-phosphorylation-of-chip-promotes-the-taif-dependent-death-pathway-in-rotenone-treated-cortical-neurons
#8
Chiho Kim, Juhyung Lee, Yeon Uk Ko, Young J Oh
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase. Its dysregulation has been implicated in various neurodegenerative diseases. We previously reported that phosphorylation of the C-terminus of the Hsc70-interacting protein (CHIP) by Cdk5 promotes truncated apoptosis-inducing factor (tAIF)-mediated neuronal death induced by oxidative stress. Here, we determined whether this Cdk5-dependent cell death signaling pathway is present in experimental models of Parkinson's disease. First, we showed that rotenone activates Cdk5 in primary cultures of cortical neurons and causes tAIF-dependent neuronal cell death...
October 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29106033/brain-5-lipoxygenase-over-expression-worsens-memory-synaptic-integrity-and-tau-pathology-in-the-p301s-mice
#9
Alana N Vagnozzi, Phillip F Giannopoulos, Domenico Praticò
Progressive accumulation of highly phosphorylated tau protein isoforms is the main feature of a group of neurodegenerative diseases collectively called tauopathies. Data from human and animal models of these diseases have shown that neuroinflammation often accompanies their pathogenesis. The 5-lipoxygenase (5LO) is an enzyme widely expressed in the brain and a source of potent pro-inflammatory mediators, while its pharmacological inhibition modulates the phenotype of a tau transgenic mouse model, the htau mice...
November 4, 2017: Aging Cell
https://www.readbyqxmd.com/read/29095844/ensemble-based-modeling-and-rigidity-decomposition-of-allosteric-interaction-networks-and-communication-pathways-in-cyclin-dependent-kinases-differentiating-kinase-clients-of-the-hsp90-cdc37-chaperone
#10
Gabrielle Stetz, Amanda Tse, Gennady M Verkhivker
The overarching goal of delineating molecular principles underlying differentiation of protein kinase clients and chaperone-based modulation of kinase activity is fundamental to understanding activity of many oncogenic kinases that require chaperoning of Hsp70 and Hsp90 systems to attain a functionally competent active form. Despite structural similarities and common activation mechanisms shared by cyclin-dependent kinase (CDK) proteins, members of this family can exhibit vastly different chaperone preferences...
2017: PloS One
https://www.readbyqxmd.com/read/29082320/%C3%AE-9-tetrahydrocannabinol-experience-influences-%C3%AE-fosb-and-downstream-gene-expression-in-prefrontal-cortex
#11
Matthew F Lazenka, Minho Kang, Dipanjana Datta De, Dana E Selley, Laura J Sim-Selley
Introduction: Repeated administration of abused drugs, including Δ(9)-tetrahydrocannabinol (THC), induces the stable transcription factor ΔFosB in dopaminergic terminal field regions of the mesolimbic system. These studies investigated the effect of prior repeated THC treatment on THC-induced ΔFosB expression and regulation of downstream targets in the forebrain. Methods: Mice received THC (10 mg/kg) or vehicle twice daily for 13 days, and then half of each group received a single injection of THC or vehicle 45 min before brain collection...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29078422/correction-for-huang-et-al-cdk5-dependent-phosphorylation-of-liprin%C3%AE-1-mediates-neuronal-activity-dependent-synapse-development
#12
(no author information available yet)
No abstract text is available yet for this article.
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29076761/cdk5-in-oncology-recent-advances-and-future-prospects
#13
Jimma Likisa Lenjisa, Solomon Tadesse, Nishat Zareen Khair, Malika Kumarasiri, Mingfeng Yu, Hugo Albrecht, Robert Milne, Shudong Wang
Selective abrogation of cyclin-dependent kinases (CDK) activity is a highly promising strategy in cancer treatment. The atypical CDK, CDK5 has long been known for its role in neurodegenerative diseases, and is becoming an attractive drug target for cancer therapy. Myriads of recent studies have uncovered that aberrant expression of CDK5 contributes to the oncogenic initiation and progression of multiple solid and hematological malignancies. CDK5 is also implicated in the regulation of cancer stem cell biology...
October 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29063115/-trpv1-an-important-molecule-involved-in-the-peripheral-sensitization-during-chronic-pain-and-central-pain-modulation
#14
Ying Zhang, Yun Wang
As chronic pain is a severe problem in clinics, study of the mechanisms of chronic pain and development of novel analgesic agents is of significance. In the past decade, our lab completed a series of studies on the regulatory mechanisms of functional sensitization and membrane trafficking of transient receptor potential vanilloid type 1 (TRPV1), a key molecule involved in the development of peripheral sensitization. Our studies elucidated the important regulatory roles of several protein kinases, including PKD1 (protein kinase D1), Cdk5 (cyclin-dependent kinase 5) and LIMK (LIM-motif containing kinase), in inflammatory thermal hyperalgesia...
October 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29062096/functional-role-of-cyclin-dependent-kinase-5-in-the-regulation-of-melanogenesis-and-epidermal-structure
#15
Changsheng Dong, Shanshan Yang, Ruiwen Fan, Kaiyuan Ji, Junzhen Zhang, Xuexian Liu, Shuaipeng Hu, Jianshan Xie, Yu Liu, Wenjun Gao, Haidong Wang, Jianbo Yao, George W Smith, Muren Herrid
The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (MITF) and paired-box 3 (PAX3) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of MITF and PAX3...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29058287/aberrant-activation-of-cdc2-cyclin-b1-is-involved-in-initiation-of-cytoskeletal-pathology-in-murine-niemann-pick-disease-type-c
#16
Li Ba, Zhi-Jun Li, Bi-Tao Bu, Wei Wang, Min Zhang
Niemann-Pick disease type C (NPC) is a fatal, neurovisceral lipid storage disease, neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons, progressive neuronal loss, neurofibrillary tangles (NFTs) formation, and axonal spheroids (AS). Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC (npc mice). With a goal of elucidating the mechanisms underlying the lesion formation, we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2, cdk4, and cdk5 in lesion formation in young npc mice...
October 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/29056962/chiglitazar-preferentially-regulates-gene-expression-via-configuration-restricted-binding-and-phosphorylation-inhibition-of-ppar%C3%AE
#17
De-Si Pan, Wei Wang, Nan-Song Liu, Qian-Jiao Yang, Kun Zhang, Jing-Zhong Zhu, Song Shan, Zhi-Bin Li, Zhi-Qiang Ning, Laiqiang Huang, Xian-Ping Lu
Type 2 diabetes mellitus is often treated with insulin-sensitizing drugs called thiazolidinediones (TZD), which improve insulin resistance and glycemic control. Despite their effectiveness in treating diabetes, these drugs provide little protection from eminent cardiovascular disease associated with diabetes. Here we demonstrate how chiglitazar, a configuration-restricted non-TZD peroxisome proliferator-activated receptor (PPAR) pan agonist with moderate transcription activity, preferentially regulates ANGPTL4 and PDK4, which are involved in glucose and lipid metabolism...
2017: PPAR Research
https://www.readbyqxmd.com/read/29036814/curcumin-ameliorates-neuroinflammation-neurodegeneration-and-memory-deficits-in-p25-transgenic-mouse-model-that-bears-hallmarks-of-alzheimer-s-disease
#18
Jeyapriya Raja Sundaram, Charlene Priscilla Poore, Noor Hazim Bin Sulaimee, Tej Pareek, Wei Fun Cheong, Markus R Wenk, Harish C Pant, Sally A Frautschy, Chian-Ming Low, Sashi Kesavapany
Several studies have indicated that neuroinflammation is indeed associated with neurodegenerative disease pathology. However, failures of recent clinical trials of anti-inflammatory agents in neurodegenerative disorders have emphasized the need to better understand the complexity of the neuroinflammatory process in order to unravel its link with neurodegeneration. Deregulation of Cyclin-dependent kinase 5 (Cdk5) activity by production of its hyperactivator p25 is involved in the formation of tau and amyloid pathology reminiscent of Alzheimer's disease (AD)...
October 12, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29031852/inhibition-of-cdk5-rejuvenates-inhibitory-circuits-and-restores-experience-dependent-plasticity-in-adult-visual-cortex
#19
Yue Li, Laijian Wang, Xinxin Zhang, Mengyao Huang, Sitong Li, Xinxing Wang, Lin Chen, Bin Jiang, Yupeng Yang
Cyclin-dependent kinase 5 (Cdk5) acts as an essential modulator for neural development and neurological disorders. Here we show that Cdk5 plays a pivotal role in modulating GABAergic signaling and the maturation of visual system. In adult mouse primary visual cortex, Cdk5 formed complex with the GABA synthetic enzyme glutamate decarboxylase GAD67, but not with GAD65. In addition to enhancement in the surface level of NR2B-containing NMDA receptors, inhibition of Cdk5 reduced the protein levels of GADs and Otx2, while leaving intact the expression of vesicular GABA transporter and subunits of GABAA or AMPA receptors...
October 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29027727/downregulated-apoptosis-and-autophagy-after-anti-a%C3%AE-immunotherapy-in-alzheimer-s-disease
#20
Claire Paquet, James Ar Nicoll, Seth Love, François Mouton-Liger, Clive Holmes, Jacques Hugon, Delphine Boche
Aβ immunisation of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunisation, we have assessed the impact of previous Aβ immunisation on the expression of a range of apoptotic proteins in post-mortem human brain tissue. Cortex from 13 AD patients immunised with AN1792 (iAD) and from 27 non-immunised AD (cAD) cases was immunolabelled for pro-apoptotic proteins implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK), activated caspase3 (a-casp3), phosphorylated GSK3β on tyrosine 216 (GSK3βtyr216 ), p53 and Cdk5/p35...
October 13, 2017: Brain Pathology
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