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961.
Mauro Rassu Alice Biosa Manuela Galioto Milena Fais Paola Sini Elisa Greggio Giovanni Piccoli Claudia Crosio Ciro Iaccarino 《Journal of cellular and molecular medicine》2019,23(12):8505-8510
Mutations in leucine‐rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD). The LRRK2 physiological and pathological function is still debated. However, different experimental evidence based on LRRK2 cellular localization and LRRK2 protein interactors suggests that LRRK2 may be part and regulate a protein network modulating vesicle dynamics/trafficking. Interestingly, the synaptic vesicle protein SV2A is part of this protein complex. Importantly, SV2A is the binding site of the levetiracetam (LEV), a compound largely used in human therapy for epilepsy treatment. The binding of LEV to SV2A reduces the neuronal firing by the modulation of vesicle trafficking although by an unclear molecular mechanism. In this short communication, we have analysed the interaction between the LRRK2 and SV2A pathways by LEV treatment. Interestingly, LEV significantly counteracts the effect of LRRK2 G2019S pathological mutant expression in three different cellular experimental models. Our data strongly suggest that LEV treatment may have a neuroprotective effect on LRRK2 pathological mutant toxicity and that LEV repositioning could be a viable compound for PD treatment. 相似文献
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963.
964.
965.
Yann Ferrandez Manuela Dezi Mickael Bosco Agathe Urvoas Marie Valerio-Lepiniec Christel Le Bon Fabrice Giusti Isabelle Broutin Grégory Durand Ange Polidori Jean-Luc Popot Martin Picard Philippe Minard 《The Journal of membrane biology》2014,247(9-10):925-940
Specific, tight-binding protein partners are valuable helpers to facilitate membrane protein (MP) crystallization, because they can i) stabilize the protein, ii) reduce its conformational heterogeneity, and iii) increase the polar surface from which well-ordered crystals can grow. The design and production of a new family of synthetic scaffolds (dubbed αReps, for “artificial alpha repeat protein”) have been recently described. The stabilization and immobilization of MPs in a functional state are an absolute prerequisite for the screening of binders that recognize specifically their native conformation. We present here a general procedure for the selection of αReps specific of any MP. It relies on the use of biotinylated amphipols, which act as a universal “Velcro” to stabilize, and immobilize MP targets onto streptavidin-coated solid supports, thus doing away with the need to tag the protein itself. 相似文献
966.
Rodrigo Acu?a Nicolás Cifuentes-Mu?oz Chantal L. Márquez Manuela Bulling Jonas Klingstr?m Roberta Mancini Pierre-Yves Lozach Nicole D. Tischler 《Journal of virology》2014,88(4):2344-2348
How hantaviruses assemble and exit infected cells remains largely unknown. Here, we show that the expression of Andes (ANDV) and Puumala (PUUV) hantavirus Gn and Gc envelope glycoproteins lead to their self-assembly into virus-like particles (VLPs) which were released to cell supernatants. The viral nucleoprotein was not required for particle formation. Further, a Gc endodomain deletion mutant did not abrogate VLP formation. The VLPs were pleomorphic, exposed protrusions and reacted with patient sera. 相似文献
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968.
Daniela Patinha Joana Afonso Teresa Sousa Manuela Morato António Albino-Teixeira 《Life sciences》2014
Aims
Activation of renal renin–angiotensin system (RAS) and reactive oxygen species (ROS) are the main pathophysiological mechanisms associated with kidney injury both in diabetes and hypertension. However, the contribution to medullary damage when the two pathologies coexist has seldom been explored.Main methods
Diabetes was induced with streptozotocin in twelve week-old male Wistar and spontaneously hypertensive rats (SHR) rats; controls received vehicle. Three weeks later, systolic blood pressure (SBP), plasma and urinary angiotensinogen (AGT), renal oxidative stress and metabolic status were evaluated.Key findings
SBP was higher in SHR-controls than in Wistar-controls (200 ± 6 and 127 ± 3 mmHg, respectively) and decreased in SHR-diabetics but not in Wistar-diabetics (143 ± 8 and 122 ± 6 mmHg, respectively). Renal medullary hydrogen peroxide (H2O2) production was similarly increased in diabetics (Wistar: 0.32 ± 0.04 and 1.11 ± 0.10 nmol/mg protein, respectively; SHR: 0.40 ± 0.05 and 0.90 ± 0.14 nmol/mg protein, respectively) and positively correlated with glycemia (Wistar: r = 0.7166, SHR: r = 0.7899, p < 0.05) and urinary AGT excretion (Wistar: r = 0.8333; SHR: r = 0.8326, p < 0.05). Cortical H2O2 production was higher in SHR-controls than in Wistar-controls (1.10 ± 0.09 and 0.26 ± 0.04 nmol/mg protein, respectively) and diabetes induction decreased it in SHR (0.70 ± 0.09 nmol/mg protein). Diabetes increased urinary AGT excretion by more than 7-fold and decreased plasma AGT concentration by more than 1.5-fold in both strains.Significance
Our results show that STZ-induced diabetes increases medullary H2O2 production and urinary AGT excretion with similar magnitude in normotensive and hypertensive animals. Reducing blood pressure attenuates hypertension-associated cortical damage but does not prevent medullary dysfunction. 相似文献969.
Water stress and recovery in the performance of two Eucalyptus globulus clones: physiological and biochemical profiles 总被引:1,自引:0,他引:1
Barbara Correia Marta Pintó‐Marijuan Lucinda Neves Ricard Brossa Maria Celeste Dias Armando Costa Bruno B. Castro Clara Araújo Conceição Santos Maria Manuela Chaves Glória Pinto 《Physiologia plantarum》2014,150(4):580-592
Eucalyptus plantations are among the most productive forest stands in Portugal and Spain, being mostly used for pulp production and, more recently, as an energy crop. However, the region's Mediterranean climate, with characteristic severe summer drought, negatively affects eucalypt growth and increases mortality. Although the physiological response to water shortage is well characterized for this species, evidence about the plants' recovery ability remains scarce. In order to assess the physiological and biochemical response of Eucalyptus globulus during the recovery phase, two genotypes (AL‐18 and AL‐10) were submitted to a 3‐week water stress period at two different intensities (18 and 25% of field capacity), followed by 1 week of rewatering. Recovery was assessed 1 day and 1 week after rehydration. Drought reduced height, biomass, water potential, NPQ and gas exchange in both genotypes. Contrarily, the levels of pigments, chlorophyll fluorescence parameters (Fv/Fm and φPSII), MDA and ABA increased. During recovery, the physiological and biochemical profile of stressed plants showed a similar trend: they experienced reversion of altered traits (MDA, ABA, E, gs, pigments), while other parameters did not recover (φPSII, NPQ). Furthermore, an overcompensation of CO2 assimilation was achieved 1 week after rehydration, which was accompanied by greater growth and re‐establishment of oxidative balance. Both genotypes were tolerant to the tested conditions, although clonal differences were found. AL‐10 was more productive and showed a more rapid and dynamic response to rehydration (namely in carotenoid content, φPSII and NPQ) compared to clone AL‐18. 相似文献
970.
Carola Stribl Aladin Samara Dietrich Trümbach Regina Peis Manuela Neumann Helmut Fuchs Valerie Gailus-Durner Martin Hrabě de Angelis Birgit Rathkolb Eckhard Wolf Johannes Beckers Marion Horsch Frauke Neff Elisabeth Kremmer Sebastian Koob Andreas S. Reichert Wolfgang Hans Jan Rozman Martin Klingenspor Michaela Aichler Axel Karl Walch Lore Becker Thomas Klopstock Lisa Glasl Sabine M. H?lter Wolfgang Wurst Thomas Floss 《The Journal of biological chemistry》2014,289(15):10769-10784
The majority of amyotrophic lateral sclerosis (ALS) cases as well as many patients suffering from frontotemporal lobar dementia (FTLD) with ubiquitinated inclusion bodies show TDP-43 pathology, the protein encoded by the TAR DNA-binding protein (Tardbp) gene. We used recombinase-mediated cassette exchange to introduce an ALS patient cDNA into the mouse Tdp-43 locus. Expression levels of human A315T TDP-43 protein were 300% elevated in heterozygotes, whereas the endogenous mouse Tdp-43 was decreased to 20% of wild type levels as a result of disturbed feedback regulation. Heterozygous TDP-43A315TKi mutants lost 10% of their body weight and developed insoluble TDP-43 protein starting as early as 3 months after birth, a pathology that was exacerbated with age. We analyzed the splicing patterns of known Tdp-43 target genes as well as genome-wide gene expression levels in different tissues that indicated mitochondrial dysfunction. In heterozygous mutant animals, we observed a relative decrease in expression of Parkin (Park2) and the fatty acid transporter CD36 along with an increase in fatty acids, HDL cholesterol, and glucose in the blood. As seen in transmission electron microscopy, neuronal cells in motor cortices of TDP-43A315TKi animals had abnormal neuronal mitochondrial cristae formation. Motor neurons were reduced to 90%, but only slight motoric impairment was detected. The observed phenotype was interpreted as a predisease model, which might be valuable for the identification of further environmental or genetic triggers of neurodegeneration. 相似文献