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1.
Binnur Eroglu Donald E. Kimbler Junfeng Pang Justin Choi Demetrius Moskophidis Nathan Yanasak Krishnan M. Dhandapani Nahid F. Mivechi 《Journal of neurochemistry》2014,130(5):626-641
Traumatic brain injury (TBI) induces severe harm and disability in many accident victims and combat‐related activities. The heat‐shock proteins Hsp70/Hsp110 protect cells against death and ischemic damage. In this study, we used mice deficient in Hsp110 or Hsp70 to examine their potential requirement following TBI. Data indicate that loss of Hsp110 or Hsp70 increases brain injury and death of neurons. One of the mechanisms underlying the increased cell death observed in the absence of Hsp110 and Hsp70 following TBI is the increased expression of reactive oxygen species‐induced p53 target genes Pig1, Pig8, and Pig12. To examine whether drugs that increase the levels of Hsp70/Hsp110 can protect cells against TBI, we subjected mice to TBI and administered Celastrol or BGP‐15. In contrast to Hsp110‐ or Hsp70i‐deficient mice that were not protected following TBI and Celastrol treatment, there was a significant improvement of wild‐type mice following administration of these drugs during the first week following TBI. In addition, assessment of neurological injury shows significant improvement in contextual and cued fear conditioning tests and beam balance in wild‐type mice that were treated with Celastrol or BGP‐15 following TBI compared to TBI‐treated mice. These studies indicate a significant role of Hsp70/Hsp110 in neuronal survival following TBI and the beneficial effects of Hsp70/Hsp110 inducers toward reducing the pathological consequences of TBI.
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Analysis of the amyloid precursor protein role in neuritogenesis reveals a biphasic SH‐SY5Y neuronal cell differentiation model 下载免费PDF全文
Joana Fernandes da Rocha Odete A. B. da Cruz e Silva Sandra Isabel Vieira 《Journal of neurochemistry》2015,134(2):288-301
The existence of an intrinsic programme controlling neuritogenesis and activated during early neuronal differentiation and regeneration stages is well established. However, the identity and role of each molecular player and event, as well as how such a programme is modified by environmental signals, remain a focus of research. The amyloid precursor protein (APP) is a neuromodulator of the developing and mature nervous system, although in a highly complex manner which is far from clear. To study APP‐induced neuritogenesis, the retinoic acid (RA)‐induced SH‐SY5Y cell differentiation model was first minutely characterized in terms of RA dose, morphological outputs and relevant biochemical markers. The findings reported here unveiled two differentiation phases for the 10 μM RA dose: 1–4 (4 days excluded) and 4–8 days, clearly defined by fold increases in the ratio between APP and acetylated Tubulin. Moreover, we describe, for the first time, a unique peak of secreted APP (sAPP)/APP ratio in the first phase. Subsequent APP and sAPP modulations confirmed that a high sAPP/APP ratio potentiates the elongation of smaller processes at the earlier neuritogenic phase. This sAPP/APP ratio drops in the second phase, as holoAPP levels increase to assist the maintenance of the longer neurites, potentially via their stabilization.
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The non‐peptidic δ‐opioid receptor agonist Tan‐67 mediates neuroprotection post‐ischemically and is associated with altered amyloid precursor protein expression,maturation and processing in mice 下载免费PDF全文
Jia‐Wei Min Yanying Liu David Wang Fangfang Qiao Hongmin Wang 《Journal of neurochemistry》2018,144(3):336-347
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Microglia modulation through external vagus nerve stimulation in a murine model of Alzheimer's disease 下载免费PDF全文
Robert Kaczmarczyk Dario Tejera Bruce J. Simon Michael T. Heneka 《Journal of neurochemistry》2018,146(1):76-85
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The β‐amyloid precursor protein (APP) has been extensively studied for its role as the precursor of the β‐amyloid protein (Aβ) of Alzheimer's disease. However, the normal function of APP remains largely unknown. This article reviews studies on the structure, expression and post‐translational processing of APP, as well as studies on the effects of APP in vitro and in vivo. We conclude that the published data provide strong evidence that APP has a trophic function. APP is likely to be involved in neural stem cell development, neuronal survival, neurite outgrowth and neurorepair. However, the mechanisms by which APP exerts its actions remain to be elucidated. The available evidence suggests that APP interacts both intracellularly and extracellularly to regulate various signal transduction mechanisms.
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p75 neurotrophin receptor interacts with and promotes BACE1 localization in endosomes aggravating amyloidogenesis 下载免费PDF全文
Khalil Saadipour Noralyn B. Mañucat‐Tan Yoon Lim Damien J. Keating Kevin S. Smith Jin‐hua Zhong Hong Liao Larisa Bobrovskaya Yan‐Jiang Wang Moses V. Chao Xin‐Fu Zhou 《Journal of neurochemistry》2018,144(3):302-317
8.
S‐allyl cysteine activates the Nrf2‐dependent antioxidant response and protects neurons against ischemic injury in vitro and in vivo 下载免费PDF全文
Huanying Shi Xu Jing Xinbing Wei Ruth G. Perez Manru Ren Xiumei Zhang Haiyan Lou 《Journal of neurochemistry》2015,133(2):298-308
Stroke is a devastating clinical condition for which an effective neuroprotective treatment is currently unavailable. S‐allyl cysteine (SAC), the most abundant organosulfur compound in aged garlic extract, has been reported to possess neuroprotective effects against stroke. However, the mechanisms underlying its beneficial effects remain poorly defined. The present study tests the hypothesis that SAC attenuates ischemic neuronal injury by activating the nuclear factor erythroid‐2‐related factor 2 (Nrf2)‐dependent antioxidant response in both in vitro and in vivo models. Our findings demonstrate that SAC treatment resulted in an increase in Nrf2 protein levels and subsequent activation of antioxidant response element pathway genes in primary cultured neurons and mice. Exposure of primary neurons to SAC provided protection against oxygen and glucose deprivation‐induced oxidative insults. In wild‐type (Nrf2+/+) mice, systemic administration of SAC attenuated middle cerebral artery occlusion‐induced ischemic damage, a protective effect not observed in Nrf2 knockout (Nrf2?/?) mice. Taken together, these findings provide the first evidence that activation of the Nrf2 antioxidant response by SAC is strongly associated with its neuroprotective effects against experimental stroke and suggest that targeting the Nrf2 pathway may provide therapeutic benefit for the treatment of stroke.
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Liraglutide is neurotrophic and neuroprotective in neuronal cultures and mitigates mild traumatic brain injury in mice 下载免费PDF全文
Ian Tamargo Vardit Rubovitch David Tweedie Nigel H. Greig 《Journal of neurochemistry》2015,135(6):1203-1217
Traumatic brain injury (TBI), a brain dysfunction for which there is no present effective treatment, is often caused by a concussive impact to the head and affects an estimated 1.7 million Americans annually. Our laboratory previously demonstrated that exendin‐4, a long‐lasting glucagon‐like peptide 1 receptor (GLP‐1R) agonist, has neuroprotective effects in cellular and animal models of TBI. Here, we demonstrate neurotrophic and neuroprotective effects of a different GLP‐1R agonist, liraglutide, in neuronal cultures and a mouse model of mild TBI (mTBI). Liraglutide promoted dose‐dependent proliferation in SH‐SY5Y cells and in a GLP‐1R over‐expressing cell line at reduced concentrations. Pre‐treatment with liraglutide rescued neuronal cells from oxidative stress‐ and glutamate excitotoxicity‐induced cell death. Liraglutide produced neurotrophic and neuroprotective effects similar to those of exendin‐4 in vitro. The cAMP/PKA/pCREB pathway appears to play an important role in this neuroprotective activity of liraglutide. Furthermore, our findings in cell culture were well‐translated in a weight drop mTBI mouse model. Post‐treatment with a clinically relevant dose of liraglutide for 7 days in mice ameliorated memory impairments caused by mTBI when evaluated 7 and 30 days post trauma. These data cross‐validate former studies of exendin‐4 and suggest that liraglutide holds therapeutic potential for the treatment of mTBI.
10.
Dimethyl fumarate treatment after traumatic brain injury prevents depletion of antioxidative brain glutathione and confers neuroprotection 下载免费PDF全文
Tobias Krämer Theresa Grob Lutz Menzel Tobias Hirnet Eva Griemert Konstantin Radyushkin Serge C. Thal Axel Methner Michael K. E. Schaefer 《Journal of neurochemistry》2017,143(5):523-533
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The physiological role of the amyloid precursor protein as an adhesion molecule in the developing nervous system 下载免费PDF全文
Lucas J. Sosa Alfredo Cáceres Sebastián Dupraz Mariana Oksdath Santiago Quiroga Alfredo Lorenzo 《Journal of neurochemistry》2017,143(1):11-29
The amyloid precursor protein (APP) is a type I transmembrane glycoprotein better known for its participation in the physiopathology of Alzheimer disease as the source of the beta amyloid fragment. However, the physiological functions of the full length protein and its proteolytic fragments have remained elusive. APP was first described as a cell‐surface receptor; nevertheless, increasing evidence highlighted APP as a cell adhesion molecule. In this review, we will focus on the current knowledge of the physiological role of APP as a cell adhesion molecule and its involvement in key events of neuronal development, such as migration, neurite outgrowth, growth cone pathfinding, and synaptogenesis. Finally, since APP is over‐expressed in Down syndrome individuals because of the extra copy of chromosome 21, in the last section of the review, we discuss the potential contribution of APP to the neuronal and synaptic defects described in this genetic condition.
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SorCS1 variants and amyloid precursor protein (APP) are co‐transported in neurons but only SorCS1c modulates anterograde APP transport 下载免费PDF全文
Guido Hermey Nadine Schmidt Björn Bluhm Daniel Mensching Kristina Ostermann Carsten Rupp Dietmar Kuhl Stefan Kins 《Journal of neurochemistry》2015,135(1):60-75
Processing of amyloid precursor protein (APP) into amyloid‐β peptide (Aβ) is crucial for the development of Alzheimer's disease (AD). Because this processing is highly dependent on its intracellular itinerary, altered subcellular targeting of APP is thought to directly affect the degree to which Aβ is generated. The sorting receptor SorCS1 has been genetically linked to AD, but the underlying molecular mechanisms are poorly understood. We analyze two SorCS1 variants; one, SorCS1c, conveys internalization of surface‐bound ligands whereas the other, SorCS1b, does not. In agreement with previous studies, we demonstrate co‐immunoprecipitation and co‐localization of both SorCS1 variants with APP. Our results suggest that SorCS1c and APP are internalized independently, although they mostly share a common post‐endocytic pathway. We introduce functional Venus‐tagged constructs to study SorCS1b and SorCS1c in living cells. Both variants are transported by fast anterograde axonal transport machinery and about 30% of anterograde APP‐positive transport vesicles contain SorCS1. Co‐expression of SorCS1b caused no change of APP transport kinetics, but SorCS1c reduced the anterograde transport rate of APP and increased the number of APP‐positive stationary vesicles. These data suggest that SorCS1 and APP share trafficking pathways and that SorCS1c can retain APP from insertion into anterograde transport vesicles.
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Neuropilin tolloid‐like 1 (Neto1), is a CUB domain‐containing transmembrane protein that was recently identified as a novel component of the NMDA receptor complex. Here, we have investigated the possible association of Neto1 with the amyloid precursor protein (APP)695/GluN1/GluN2A and APP695/GluN1/GluN2B NMDA receptor trafficking complexes that we have previously identified. Neto1HA was shown to co‐immunoprecipitate with assembled NMDA receptors via GluN2A or GluN2B subunits; Neto1HA did not co‐immunoprecipitate APP695FLAG. Co‐immunoprecipitations from mammalian cells co‐transfected with APP695FLAG, Neto1HA and GluN1/GluN2A or GluN1/GluN2B revealed that all four proteins co‐exist within one macromolecular complex. Immunoprecipitations from native brain tissue similarly revealed the existence of a GluN1/GluN2A or GluN2B/APP/Neto1 complex. Neto1HA caused a reduction in the surface expression of both NMDA receptor subtypes, but had no effect on APP695FLAG‐ or PSD‐95αc‐Myc enhanced surface receptor expression. The Neto1 binding domain of GluN2A was mapped using GluN1/GluN2A chimeras and GluN2A truncation constructs. The extracellular GluN2A domain does not contribute to association with Neto1HA but deletion of the intracellular tail resulted in a loss of Neto‐1HA co‐immunoprecipitation which was paralleled by a loss of association between GluN2A and SAP102. Thus, Neto1 is concluded to be a component of APP/NMDA receptor trafficking complexes.
15.
Till B. Puschmann Carl Zandén Isabell Lebkuechner Camille Philippot Yolanda de Pablo Johan Liu Milos Pekny 《Journal of neurochemistry》2014,128(6):878-889
Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF), a vascular‐derived trophic factor, belongs to the epidermal growth factor (EGF) family of neuroprotective, hypoxia‐inducible proteins released by astrocytes in CNS injuries. It was suggested that HB–EGF can replace fetal calf serum (FCS) in astrocyte cultures. We previously demonstrated that in contrast to standard 2D cell culture systems, Bioactive3D culture system, when used with FCS, minimizes the baseline activation of astrocytes and preserves their complex morphology. Here, we show that HB‐EGF induced EGF receptor (EGFR) activation by Y1068 phosphorylation, Mapk/Erk pathway activation, and led to an increase in cell proliferation, more prominent in Bioactive3D than in 2D cultures. HB‐EGF changed morphology of 2D and Bioactive3D cultured astrocytes toward a radial glia‐like phenotype and induced the expression of intermediate filament and progenitor cell marker protein nestin. Glial fibrillary acidic protein (GFAP) and vimentin protein expression was unaffected. RT‐qPCR analysis demonstrated that HB‐EGF affected the expression of Notch signaling pathway genes, implying a role for the Notch signaling in HB‐EGF‐mediated astrocyte response. HB‐EGF can be used as a FCS replacement for astrocyte expansion and in vitro experimentation both in 2D and Bioactive3D culture systems; however, caution should be exercised since it appears to induce partial de‐differentiation of astrocytes.
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Cocaine‐ and amphetamine‐regulated transcript peptide in the nucleus accumbens shell inhibits cocaine‐induced locomotor sensitization to transient over‐expression of α‐Ca2+/calmodulin‐dependent protein kinase II 下载免费PDF全文
Lixia Xiong Qing Meng Xi Sun Xiangtong Lu Qiang Fu Qinghua Peng Jianhua Yang Ki‐Wan Oh Zhenzhen Hu 《Journal of neurochemistry》2018,146(3):289-303
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Anne M. Nixon Mark D. Meadowcroft Elizabeth B. Neely Amanda M. Snyder Carson J. Purnell Justin Wright Regina Lamendella Wint Nandar Xuemei Huang James R. Connor 《Journal of neurochemistry》2018,145(4):299-311
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Juan G. Zarruk María I. Cuartero Iván Ballesteros Guadalupe Camarero Ana Moraga Jesús M. Pradillo María A. Moro Ignacio Lizasoain 《Journal of neurochemistry》2013,126(6):819-826
CDP‐choline has shown neuroprotective effects in cerebral ischemia. In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP‐choline and placebo groups, CDP‐choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t‐PA. Several mechanisms have been proposed to explain the beneficial actions of CDP‐choline. We have now studied the participation of Sirtuin1 (SIRT1) in the neuroprotective actions of CDP‐choline. Fischer rats and Sirt1?/? mice were subjected to permanent focal ischemia. CDP‐choline (0.2 or 2 g/kg), sirtinol (a SIRT1 inhibitor; 10 mg/kg), and resveratrol (a SIRT1 activator; 2.5 mg/kg) were administered intraperitoneally. Brains were removed 24 and 48 h after ischemia for western blot analysis and infarct volume determination. Treatment with CDP‐choline increased SIRT1 protein levels in brain concomitantly to neuroprotection. Treatment with sirtinol blocked the reduction in infarct volume caused by CDP‐choline, whereas resveratrol elicited a strong synergistic neuroprotective effect with CDP‐choline. CDP‐choline failed to reduce infarct volume in Sirt1?/? mice. Our present results demonstrate a robust effect of CDP‐choline like SIRT1 activator by up‐regulating its expression. Our findings suggest that therapeutic strategies to activate SIRT1 may be useful in the treatment of stroke.
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Giannina Descalzi Tao Chen Kohei Koga Xiang‐Yao Li Kaori Yamada Min Zhuo 《Journal of neurochemistry》2013,126(5):636-650
Recent investigations into the mechanisms mediating itch transmission have focused on spinal mechanisms, whereas few studies have investigated the role of the cerebral cortex in itch‐related behaviors. Human imaging studies show that several cortical regions are active in correspondence with itch, including the anterior cingulate cortex (ACC). We present here evidence of cortical modulation of pruritogen‐induced scratching behavior. We combine pharmacological, genetic, and electrophysiological approaches to show that cortical GluK1‐containing kainate (KA) receptors are involved in scratching induced by histamine and non‐histamine‐dependent itching stimuli. We further show that scratching corresponds with enhanced excitatory transmission in the ACC through KA receptor modulation of inhibitory circuitry. In addition, we found that inhibiting GluK1‐containing KA receptors in the ACC also reduced behavioral nociceptive responses induced by formalin. Our results reveal a new role of the cortex in pruritogen‐induced scratching.
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Single cocaine exposure does not alter striatal pre‐synaptic dopamine function in mice: an [18F]‐FDOPA PET study 下载免费PDF全文
David R Bonsall Michelle Kokkinou Mattia Veronese Christopher Coello Lisa A. Wells Oliver D. Howes 《Journal of neurochemistry》2017,143(5):551-560