Database : MEDLINE
Search on : brain [Words]
References found : 1242250 [refine]
Displaying: 1 .. 10   in format [Detailed]

page 1 of 124225 go to page                         

  1 / 1242250 MEDLINE  
              next record last record
select
to print
Photocopy
Full text

[PMID]: 25159276
[Au] Autor:Maguire CA; Ramirez SH; Merkel SF; Sena-Esteves M; Breakefield XO
[Ad] Address:Department of Neurology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, Molecular Neurogenetics Unit, 13th Street, Building 149, Charlestown, MA, 02129, USA, cmaguire@mgh.harvard.edu.
[Ti] Title:Gene therapy for the nervous system: challenges and new strategies.
[So] Source:Neurotherapeutics;11(4):817-39, 2014 Oct.
[Is] ISSN:1878-7479
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Current clinical treatments for central nervous system (CNS) diseases, such as Parkinson's disease and glioblastoma do not halt disease progression and have significant treatment morbidities. Gene therapy has the potential to "permanently" correct disease by bringing in a normal gene to correct a mutant gene deficiency, knocking down mRNA of mutant alleles, and inducing cell-death in cancer cells using transgenes encoding apoptosis-inducing proteins. Promising results in clinical trials of eye disease (Leber's congenital aumorosis) and Parkinson's disease have shown that gene-based neurotherapeutics have great potential. The recent development of genome editing technology, such as zinc finger nucleases, TALENS, and CRISPR, has made the ultimate goal of gene correction a step closer. This review summarizes the challenges faced by gene-based neurotherapeutics and the current and recent strategies designed to overcome these barriers. We have chosen the following challenges to focus on in this review: (1) delivery vehicles (both virus and nonviral), (2) use of promoters for vector-mediated gene expression in CNS, and (3) delivery across the blood-brain barrier. The final section (4) focuses on promising pre-clinical/clinical studies of neurotherapeutics.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1007/s13311-014-0299-5

  2 / 1242250 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 25155315
[Au] Autor:Dauer W
[Ad] Address:Department of Neurology, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, 48109-220, USA, dauer@med.umich.edu.
[Ti] Title:Inherited isolated dystonia: clinical genetics and gene function.
[So] Source:Neurotherapeutics;11(4):807-16, 2014 Oct.
[Is] ISSN:1878-7479
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Isolated inherited dystonia-formerly referred to as primary dystonia-is characterized by abnormal motor functioning of a grossly normal appearing brain. The disease manifests as abnormal involuntary twisting movements. The absence of overt neuropathological lesions, while intriguing, has made it particularly difficult to unravel the pathogenesis of isolated inherited dystonia. The explosion of genetic techology enabling the identification of the causative gene mutations is transforming our understanding of dystonia pathogenesis, as the molecular, cellular and circuit level consequences of these mutations are identified in experimental systems. Here, I review the clinical genetics and cell biology of three forms of inherited dystonia for which the causative mutation is known: DYT1 (TOR1A), DYT6 (THAP1), DYT25 (GNAL).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1007/s13311-014-0297-7

  3 / 1242250 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 24962319
[Au] Autor:Kim Y; Kumar S
[Ad] Address:Department of Bioengineering, University of California, Berkeley, California.
[Ti] Title:CD44-Mediated Adhesion to Hyaluronic Acid Contributes to Mechanosensing and Invasive Motility.
[So] Source:Mol Cancer Res;12(10):1416-29, 2014 Oct.
[Is] ISSN:1557-3125
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UNLABELLED: The high-molecular-weight glycosaminoglycan, hyaluronic acid (HA), makes up a significant portion of the brain extracellular matrix. Glioblastoma multiforme (GBM), a highly invasive brain tumor, is associated with aberrant HA secretion, tissue stiffening, and overexpression of the HA receptor CD44. Here, transcriptomic analysis, engineered materials, and measurements of adhesion, migration, and invasion were used to investigate how HA/CD44 ligation contributes to the mechanosensing and invasive motility of GBM tumor cells, both intrinsically and in the context of Arg-Gly-Asp (RGD) peptide/integrin adhesion. Analysis of transcriptomic data from The Cancer Genome Atlas reveals upregulation of transcripts associated with HA/CD44 adhesion. CD44 suppression in culture reduces cell adhesion to HA on short time scales (0.5-hour postincubation) even if RGD is present, whereas maximal adhesion on longer time scales (3 hours) requires both CD44 and integrins. Moreover, time-lapse imaging demonstrates that cell adhesive structures formed during migration on bare HA matrices are more short lived than cellular protrusions formed on surfaces containing RGD. Interestingly, adhesion and migration speed were dependent on HA hydrogel stiffness, implying that CD44-based signaling is intrinsically mechanosensitive. Finally, CD44 expression paired with an HA-rich microenvironment maximized three-dimensional invasion, whereas CD44 suppression or abundant integrin-based adhesion limited it. These findings demonstrate that CD44 transduces HA-based stiffness cues, temporally precedes integrin-based adhesion maturation, and facilitates invasion. IMPLICATIONS: This study reveals that the CD44 receptor, which is commonly overexpressed in GBM tumors, is critical for cell adhesion, invasion, and mechanosensing of an HA-based matrix. Mol Cancer Res; 12(10); 1416-29. ©2014 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/1541-7786.MCR-13-0629

  4 / 1242250 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 24777168
[Au] Autor:Bendjilali N; Nelson J; Weinsheimer S; Sidney S; Zaroff JG; Hetts SW; Segal M; Pawlikowska L; McCulloch CE; Young WL; Kim H
[Ad] Address:Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California, USA Kaiser Permanente of Northern California, Division of Research, Oakland, California, USA....
[Ti] Title:Common variants on 9p21.3 are associated with brain arteriovenous malformations with accompanying arterial aneurysms.
[So] Source:J Neurol Neurosurg Psychiatry;85(11):1280-3, 2014 Nov.
[Is] ISSN:1468-330X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To investigate whether previously reported 9p21.3 single nucleotide polymorphisms (SNPs) are associated with risk of brain arteriovenous malformations (BAVM), which often have accompanying arterial aneurysms. Common variants in the 9p21.3 locus have been reported to be associated with multiple cardiovascular phenotypes, including coronary artery disease and intracranial aneurysms (rs10757278 and rs1333040). METHODS: We used data from 338 BAVM cases participating in the University of California, San Francisco (UCSF)-Kaiser Brain AVM Study Project and 504 healthy controls to evaluate genotypes for seven common SNPs (minor allele frequency>0.05) that were imputed using 1000 Genomes Phase 1 European data (R(2)>0.87). Association with BAVM was tested using logistic regression adjusting for age, sex and the top three principal components of ancestry. Subgroup analysis included 205 BAVM cases with aneurysm data: 74 BAVM with aneurysm versus 504 controls and 131 BAVM without aneurysm versus 504 controls. RESULTS: We observed suggestive association with BAVM and rs10757278-G (OR=1.23, 95% CI 0.99 to 1.53, p=0.064) and rs1333040-T (OR=1.27, 95% CI 1.01 to 1.58, p=0.04). For rs10757278-G, the association was stronger in BAVM cases with aneurysm (OR=1.52, 95% CI 1.03 to 2.22, p=0.032) than in BAVM without aneurysm (OR=0.98, 95% CI 0.72 to 1.34, p=0.91). Similar patterns of effects were observed for rs1333040 and for other SNPs in linkage disequilibrium (r(2)>0.8) with rs10757278. CONCLUSIONS: Common 9p21.3 variants showed similar effect sizes for association with BAVM as previously reported for aneurysmal disease. The association with BAVM appears to be explained by known associations with aneurysms, suggesting that BAVM-associated aneurysms share similar vascular pathology mechanisms with other aneurysm types.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1136/jnnp-2013-306461

  5 / 1242250 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 25193658
[Au] Autor:Jin H; Chiou TT; Serwanski DR; Miralles CP; Pinal N; De Blas AL
[Ad] Address:From the Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269....
[Ti] Title:Ring Finger Protein 34 (RNF34) Interacts with and Promotes γ-Aminobutyric Acid Type-A Receptor Degradation via Ubiquitination of the γ2 Subunit.
[So] Source:J Biol Chem;289(42):29420-36, 2014 Oct 17.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We have found that the large intracellular loop of the γ2 GABAA receptor (R) subunit (γ2IL) interacts with RNF34 (an E3 ubiquitin ligase), as shown by yeast two-hybrid and in vitro pulldown assays. In brain extracts, RNF34 co-immunoprecipitates with assembled GABAARs. In co-transfected HEK293 cells, RNF34 reduces the expression of the γ2 GABAAR subunit by increasing the ratio of ubiquitinated/nonubiquitinated γ2. Mutating several lysines of the γ2IL into arginines makes the γ2 subunit resistant to RNF34-induced degradation. RNF34 also reduces the expression of the γ2 subunit when α1 and ß3 subunits are co-assembled with γ2. This effect is partially reversed by leupeptin or MG132, indicating that both the lysosomal and proteasomal degradation pathways are involved. Immunofluorescence of cultured hippocampal neurons shows that RNF34 forms clusters and that a subset of these clusters is associated with GABAergic synapses. This association is also observed in the intact rat brain by electron microscopy immunocytochemistry. RNF34 is not expressed until the 2nd postnatal week of rat brain development, being highly expressed in some interneurons. Overexpression of RNF34 in hippocampal neurons decreases the density of γ2 GABAAR clusters and the number of GABAergic contacts that these neurons receive. Knocking down endogenous RNF34 with shRNA leads to increased γ2 GABAAR cluster density and GABAergic innervation. The results indicate that RNF34 regulates postsynaptic γ2-GABAAR clustering and GABAergic synaptic innervation by interacting with and ubiquitinating the γ2-GABAAR subunit promoting GABAAR degradation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1074/jbc.M114.603068

  6 / 1242250 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 25190810
[Au] Autor:Velázquez-Marrero C; Seale GE; Treistman SN; Martin GE
[Ad] Address:the Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico 00901....
[Ti] Title:Large Conductance Voltage- and Ca2+-gated Potassium (BK) Channel ß4 Subunit Influences Sensitivity and Tolerance to Alcohol by Altering Its Response to Kinases.
[So] Source:J Biol Chem;289(42):29261-72, 2014 Oct 17.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Tolerance is a well described component of alcohol abuse and addiction. The large conductance voltage- and Ca(2+)-gated potassium channel (BK) has been very useful for studying molecular tolerance. The influence of association with the ß4 subunit can be observed at the level of individual channels, action potentials in brain slices, and finally, drinking behavior in the mouse. Previously, we showed that 50 mm alcohol increases both α and αß4 BK channel open probability, but only α BK develops acute tolerance to this effect. Currently, we explore the possibility that the influence of the ß4 subunit on tolerance may result from a striking effect of ß4 on kinase modulation of the BK channel. We examine the influence of the ß4 subunit on PKA, CaMKII, and phosphatase modulation of channel activity, and on molecular tolerance to alcohol. We record from human BK channels heterologously expressed in HEK 293 cells composed of its core subunit, α alone (Insertless), or co-expressed with the ß4 BK auxiliary subunit, as well as, acutely dissociated nucleus accumbens neurons using the cell-attached patch clamp configuration. Our results indicate that BK channels are strongly modulated by activation of specific kinases (PKA and CaMKII) and phosphatases. The presence of the ß4 subunit greatly influences this modulation, allowing a variety of outcomes for BK channel activity in response to acute alcohol.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1074/jbc.M114.604306

  7 / 1242250 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 25190809
[Au] Autor:Kang Y; Ge Y; Cassidy RM; Lam V; Luo L; Moon KM; Lewis R; Molday RS; Wong RO; Foster LJ; Craig AM
[Ad] Address:From the Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver V6T 2B5, Canada....
[Ti] Title:A combined transgenic proteomic analysis and regulated trafficking of neuroligin-2.
[So] Source:J Biol Chem;289(42):29350-64, 2014 Oct 17.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Synapses, the basic units of communication in the brain, require complex molecular machinery for neurotransmitter release and reception. Whereas numerous components of excitatory postsynaptic sites have been identified, relatively few proteins are known that function at inhibitory postsynaptic sites. One such component is neuroligin-2 (NL2), an inhibitory synapse-specific cell surface protein that functions in cell adhesion and synaptic organization via binding to neurexins. In this study, we used a transgenic tandem affinity purification and mass spectrometry strategy to isolate and characterize NL2-associated complexes. Complexes purified from brains of transgenic His6-FLAG-YFP-NL2 mice showed enrichment in the Gene Ontology terms cell-cell signaling and synaptic transmission relative to complexes purified from wild type mice as a negative control. In addition to expected components including GABA receptor subunits and gephyrin, several novel proteins were isolated in association with NL2. Based on the presence of multiple components involved in trafficking and endocytosis, we showed that NL2 undergoes dynamin-dependent endocytosis in response to soluble ligand and colocalizes with VPS35 retromer in endosomes. Inhibitory synapses in brain also present a particular challenge for imaging. Whereas excitatory synapses on spines can be imaged with a fluorescent cell fill, inhibitory synapses require a molecular tag. We find the His6-FLAG-YFP-NL2 to be a suitable tag, with the unamplified YFP signal localizing appropriately to inhibitory synapses in multiple brain regions including cortex, hippocampus, thalamus, and basal ganglia. Altogether, we characterize NL2-associated complexes, demonstrate regulated trafficking of NL2, and provide tools for further proteomic and imaging studies of inhibitory synapses.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1074/jbc.M114.549279

  8 / 1242250 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 25183005
[Au] Autor:Liu X; He F; Pang R; Zhao D; Qiu W; Shan K; Zhang J; Lu Y; Li Y; Wang Y
[Ad] Address:From the Department of Microbiology and Immunology, Nanjing Medical University, Hanzhong Road 140, Nanjing, Jiangsu 210029, China....
[Ti] Title:Interleukin-17 (IL-17)-induced MicroRNA 873 (miR-873) Contributes to the Pathogenesis of Experimental Autoimmune Encephalomyelitis by Targeting A20 Ubiquitin-editing Enzyme.
[So] Source:J Biol Chem;289(42):28971-86, 2014 Oct 17.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Interleukin 17 (IL-17), produced mainly by T helper 17 (Th17) cells, is increasingly recognized as a key regulator in various autoimmune diseases, including human multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Although several microRNAs (miRNAs) with aberrant expression have been shown to contribute to the pathogenesis of MS and EAE, the mechanisms underlying the regulation of abnormal miRNA expression in astrocytes upon IL-17 stimulation remain unclear. In the present study, we detected the changes of miRNA expression profiles both in the brain tissue of EAE mice and in cultured mouse primary astrocytes stimulated with IL-17 and identified miR-873 as one of the co-up-regulated miRNAs in vivo and in vitro. The overexpression of miR-873, demonstrated by targeting A20 (TNFα-induced protein 3, TNFAIP3), remarkably reduced the A20 level and promoted NF-κB activation in vivo and in vitro as well as increasing the production of inflammatory cytokines and chemokines (i.e. IL-6, TNF-α, MIP-2, and MCP-1/5). More importantly, silencing the endogenous miR-873 or A20 gene with lentiviral vector of miR-873 sponge (LV-miR-873 sponge) or short hairpin RNA (shRNA) of A20 (LV-A20 shRNA) in vivo significantly lessened or aggravated inflammation and demyelination in the central nervous system (CNS) of EAE mice, respectively. Taken together, these findings indicate that miR-873 induced by IL-17 stimulation promotes the production of inflammatory cytokines and aggravates the pathological process of EAE mice through the A20/NF-κB pathway, which provides a new insight into the mechanism of inflammatory damage in MS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1074/jbc.M114.577429

  9 / 1242250 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 25172509
[Au] Autor:Huyghe D; Nakamura Y; Terunuma M; Faideau M; Haydon P; Pangalos MN; Moss SJ
[Ad] Address:From the Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111....
[Ti] Title:Glutamine Synthetase Stability and Subcellular Distribution in Astrocytes Are Regulated by γ-Aminobutyric Type B Receptors.
[So] Source:J Biol Chem;289(42):28808-15, 2014 Oct 17.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Emerging evidence suggests that functional γ-aminobutyric acid B receptors (GABABRs) are expressed by astrocytes within the mammalian brain. GABABRs are heterodimeric G-protein-coupled receptors that are composed of R1/R2 subunits. To date, they have been characterized in neurons as the principal mediators of sustained inhibitory signaling; however their roles in astrocytic physiology have been ill defined. Here we reveal that the cytoplasmic tail of the GABABR2 subunit binds directly to the astrocytic protein glutamine synthetase (GS) and that this interaction determines the subcellular localization of GS. We further demonstrate that the binding of GS to GABABR2 increases the steady state expression levels of GS in heterologous cells and in mouse primary astrocyte culture. Mechanistically this increased stability of GS in the presence of GABABR2 occurs via reduced proteasomal degradation. Collectively, our results suggest a novel role for GABABRs as regulators of GS stability. Given the critical role that GS plays in the glutamine-glutamate cycle, astrocytic GABABRs may play a critical role in supporting both inhibitory and excitatory neurotransmission.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1074/jbc.M114.583534

  10 / 1242250 MEDLINE  
              first record previous record
select
to print
Photocopy
Full text

[PMID]: 24997849
[Au] Autor:Shi M; Liu C; Cook TJ; Bullock KM; Zhao Y; Ginghina C; Li Y; Aro P; Dator R; He C; Hipp MJ; Zabetian CP; Peskind ER; Hu SC; Quinn JF; Galasko DR; Banks WA; Zhang J
[Ad] Address:Department of Pathology, University of Washington School of Medicine, 325 9th Ave, HMC Box 359635, Seattle, WA, 98104, USA, mshi70@u.washington.edu.
[Ti] Title:Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson's disease.
[So] Source:Acta Neuropathol;128(5):639-50, 2014 Nov.
[Is] ISSN:1432-0533
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:Extracellular α-synuclein is important in the pathogenesis of Parkinson's disease (PD) and also as a potential biomarker when tested in the cerebrospinal fluid (CSF). The performance of blood plasma or serum α-synuclein as a biomarker has been found to be inconsistent and generally ineffective, largely due to the contribution of peripherally derived α-synuclein. In this study, we discovered, via an intracerebroventricular injection of radiolabeled α-synuclein into mouse brain, that CSF α-synuclein was readily transported to blood, with a small portion being contained in exosomes that are relatively specific to the central nervous system (CNS). Consequently, we developed a technique to evaluate the levels of α-synuclein in these exosomes in individual plasma samples. When applied to a large cohort of clinical samples (267 PD, 215 controls), we found that in contrast to CSF α-synuclein concentrations, which are consistently reported to be lower in PD patients compared to controls, the levels of plasma exosomal α-synuclein were substantially higher in PD patients, suggesting an increased efflux of the protein to the peripheral blood of these patients. Furthermore, although no association was observed between plasma exosomal and CSF α-synuclein, a significant correlation between plasma exosomal α-synuclein and disease severity (r = 0.176, p = 0.004) was observed, and the diagnostic sensitivity and specificity achieved by plasma exosomal α-synuclein were comparable to those determined by CSF α-synuclein. Further studies are clearly needed to elucidate the mechanism involved in the transport of CNS α-synuclein to the periphery, which may lead to a more convenient and robust assessment of PD clinically.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1007/s00401-014-1314-y


page 1 of 124225 go to page                         
   


Refine the search
  Database : MEDLINE Advanced form   

    Search in field  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/PAHO/WHO - Latin American and Caribbean Center on Health Sciences Information