Abstract:
:With the aging of population, neurological disorders, and especially disorders involving defects in protein conformation (also known as proteopathies) pose a serious socio-economic problem. So far there is no effective treatment for most proteopathies, including Parkinson's disease (PD). The mechanism underlying PD pathogenesis is largely unknown, and the hallmark proteins, α-synuclein (SYN) and tubulin polymerization promoting protein (TPPP/p25) are challenging drug targets. These proteins are intrinsically disordered with high conformational plasticity, and have diverse physiological and pathological functions. In the healthy brain, SYN and TPPP/p25 occur in neurons and oligodendrocytes, respectively; however, in PD and multiple system atrophy, they are co-enriched and co-localized in both cell types, thereby marking pathogenesis. Although large inclusions appear at a late disease stage, small, soluble assemblies of SYN promoted by TPPP/p25 are pathogenic. In the light of these issues, we established a new innovative strategy for the validation of a specific drug target based upon the identification of contact surfaces of the pathological SYN-TPPP/p25 complex that may lead to the development of peptidomimetic foldamers suitable for pharmaceutical intervention.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Oláh J,Ovádi Jdoi
10.1002/1873-3468.13464subject
Has Abstractpub_date
2019-07-01 00:00:00pages
1641-1653issue
13eissn
0014-5793issn
1873-3468journal_volume
593pub_type
杂志文章,评审相关文献
FEBS LETTERS文献大全abstract::The mitochondrial permeability transition pore, a cyclosporin A-sensitive channel, is controlled by the transmembrane electric potential difference across the inner membrane. Here, we show that treatment of rat liver mitochondria with the arginine reagent phenylglyoxal inhibits the permeability transition pore trigger...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/s0014-5793(97)00549-8
更新日期:1997-06-16 00:00:00
abstract::A developmentally regulated exon has been identified in the 5'-alternatively spliced region of the human fast Troponin T (TnT) gene. Expressed in fetal (but not adult) muscle, this exon is homologous with the fetal exons recently described in the rabbit and rat fast TnT genes. They all exhibit a split codon organizati...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(94)00729-2
更新日期:1994-08-15 00:00:00
abstract::In plants exposed to high irradiances of visible light, the D1 protein in the reaction center of photosystem II is oxidatively damaged and rapidly degraded. Earlier work in our laboratory showed that the serine protease Deg2 performs the primary cleavage of photodamaged D1 protein in vitro. Here, we demonstrate that t...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/j.febslet.2006.11.058
更新日期:2006-12-22 00:00:00
abstract::The tissue inhibitors of matrix metalloproteinases (MMPs), TIMP-1 and TIMP-2, are also angiogenesis inhibitors. Cathepsin B and MMPs are found at sites of neovascularization in pathologies such as cancer and osteoarthritis. Treatment of TIMP-1, TIMP-2, and of a mixture of both inhibitors from human articular chondrocy...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/s0014-5793(99)00897-2
更新日期:1999-07-23 00:00:00
abstract::Calpastatin molecule contains four repeated inhibition domains, each having highly conserved internal regions A, B and C. The synthetic oligopeptides of regions A and C had no calpain inhibition activity while region B oligopeptide showed weak inhibition activity. Real-time biomolecular interaction analysis using a BI...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(95)00219-y
更新日期:1995-03-27 00:00:00
abstract::Rubrivivax gelatinosus is a facultative phototrophic non-sulfur bacterium belonging to the beta subclass of the purple bacteria. A terbutryn-resistant mutant of R. gelatinosus has been isolated and characterized. Increased resistance levels to terbutryn (300-fold), atrazine (6-fold) and o-phenanthroline (3-fold) were ...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(95)01055-j
更新日期:1995-10-23 00:00:00
abstract::Actin filaments copolymerized with both intact and chemically modified actin monomers restored their sliding activity when they were supplemented with tropomyosin extracted from skeletal muscle. In contrast, the ATPase activation of the copolymers was decreased when supplemented with tropomyosin. The results indicate ...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(96)00218-9
更新日期:1996-03-25 00:00:00
abstract::RNA binding motif protein 5 (RBM5) is a candidate tumor suppressor gene. Recent studies showed that RBM5 functions as an alternative splicing regulator of apoptosis-related genes. Here, we identify DHX15 and PRP19, two spliceosome components, as novel RBM5-interacting partners. We then show that the G-patch domain of ...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/j.febslet.2012.02.052
更新日期:2012-04-05 00:00:00
abstract::Transfer RNAs (tRNAs) are ancient macromolecules that have evolved under various environmental pressures as adaptors in translation in all forms of life but also towards alternative structures and functions. The present knowledge on both "canonical" and "deviating" signature motifs retrieved from vertical and horizont...
journal_title:FEBS letters
pub_type: 杂志文章,评审
doi:10.1016/j.febslet.2009.11.050
更新日期:2010-01-21 00:00:00
abstract::We tested the truncated 7-37 glucagon-like peptide 1 (TGLP-1), a naturally occurring porcine intestinal peptide, and other members of the glucagon family, including pancreatic glucagon (G-29), GLP-1 and GLP-2 for their ability to activate the cAMP generating system in rat gastric glands and HGT-1 human gastric cancer ...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(88)80297-7
更新日期:1988-08-15 00:00:00
abstract::Temperature-induced order/disorder transition profiles were obtained from the membranes of intact Gram-negative bacterial cells by FT-IR analysis of the frequency shifts of the acyl chain methylene symmetric stretching band as a monitor. Cells grown at different temperatures yielded distinct transition profiles. At th...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(91)81339-a
更新日期:1991-12-02 00:00:00
abstract::We focused on the functional involvement of transforming growth factor-beta-activated kinase 1 (TAK1) in transcriptional regulation of interleukin-2 (IL-2) in T cells. Costimulation of Jurkat cells with 12-O-tetradecanoylphorbol-13-acetate and A23187 leads to a rapid phosphorylation of TAK1 and TAK1-binding protein 1 ...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/j.febslet.2005.10.059
更新日期:2005-12-05 00:00:00
abstract::Disulfide bond formation is a critical step in the folding of many secretory proteins. In bacteria, disulfide bonds are introduced by the periplasmic dithiol oxidase DsbA, which transfers its catalytic disulfide bond to folding polypeptides. Reduced DsbA is reoxidized by ubiquinone Q8, catalyzed by inner membrane quin...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/j.febslet.2008.07.063
更新日期:2008-10-15 00:00:00
abstract::Chronic inflammation associated with tumor necrosis factor (TNF)-alpha and reactive oxygen species (ROS) is the hallmark of tuberculosis. Mycobacterium tuberculosis (MTB) directly stimulates human monocytes to secrete TNF-alpha. We show the augmented expression of TNF-alpha mRNA in MTB-infected monocytes by cellular a...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/j.febslet.2006.03.071
更新日期:2006-05-01 00:00:00
abstract::The Protein Data Bank (PDB) was established in 1971 as a repository for the three dimensional structures of biological macromolecules. Since then, more than 85000 biological macromolecule structures have been determined and made available in the PDB archive. Through analysis of the corpus of data, it is possible to id...
journal_title:FEBS letters
pub_type: 杂志文章,评审
doi:10.1016/j.febslet.2012.12.029
更新日期:2013-04-17 00:00:00
abstract::The timely and reliable processing of auditory and vestibular information within the inner ear requires highly sophisticated sensory transduction pathways. On a cellular level, these demands are met by hair cells, which respond to sound waves - or alterations in body positioning - by releasing glutamate-filled synapti...
journal_title:FEBS letters
pub_type: 杂志文章,评审
doi:10.1002/1873-3468.13258
更新日期:2018-11-01 00:00:00
abstract::Caspase-11 plays a crucial role in both inflammation and apoptosis. Caspase-11 not only activates caspase-1, that is required for the maturation of proinflammatory cytokines such as interleukin (IL)-1 and IL-18, but also activates caspase-3, leading to cellular apoptosis under pathological conditions. Here, we cloned ...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/s0014-5793(01)02975-1
更新日期:2001-10-26 00:00:00
abstract::Hypohalous acids are poor one-electron oxidizing agents, such that reactions with hydrogen peroxide to yield radical species are not feasible. However, the oxidation of superoxide by hypohalous acids can be a source of hydroxyl or haline radicals. The oxidation of nitrogen monoxide by hypochlorous acid is favourable, ...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(94)00494-3
更新日期:1994-06-20 00:00:00
abstract::Statistically significant similarity was revealed between amino acid sequences of NTP-binding pattern-containing domains which are among the most conserved protein segments in dissimilar groups of ss and dsDNA viruses (papova-, parvo-, geminiviruses and P4 bacteriophage), and RNA viruses (picorna-, como- and nepovirus...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(90)80175-i
更新日期:1990-03-12 00:00:00
abstract::In Xenopus prophase-blocked oocytes, it is assumed that progesterone interacts with the plasma membrane to initiate a signalling cascade that ultimately leads to MPF activation. Progesterone regulates negatively the cAMP pathway through an inhibition of adenylate cyclase. However, the mechanisms linking the initial ac...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(95)01183-f
更新日期:1995-11-20 00:00:00
abstract::Sialic acids comprise a family of terminal sugars essential for a variety of biological recognition systems. UDP-N-acetylglucosamine 2-epimerase catalyzes the first step of their biosynthesis. Periodate-oxidized UDP-N-acetylglucosamine, namely 2',3'-dialdehydo-UDP-alpha-D-N-acetylglucosamine, was found to be an effect...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/s0014-5793(02)02856-9
更新日期:2002-06-19 00:00:00
abstract::To better understand the outcome of the interaction between TNF-related apoptosis-inducing factor (TRAIL) and tumor cells, we studied TRAIL-resistant melanoma cells resulting from prolonged exposure to TRAIL and found that they had higher proliferative activity than the parental cells both in vitro and in vivo. This w...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/j.febslet.2005.02.041
更新日期:2005-03-28 00:00:00
abstract::The tailspike protein (TSP) of bacteriophage P22 is a homotrimeric multifunctional protein responsible for cell attachment and hydrolysis of the Salmonella typhimurium host cell receptor. Despite the folding of TSP involves the formation of thermolabile intermediates, the mature protein is extremely resistant to heat ...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/s0014-5793(98)00876-x
更新日期:1998-08-07 00:00:00
abstract::NG-Methyl-L-arginine (L-NMA) and NG-nitro-L-arginine (L-NNA) inhibited NO-induced cGMP accumulation in porcine aortic endothelial cells with half-maximally effective concentrations of 15 and 3.4 microM, respectively. The effects of both compounds were reversible, but the L-NNA-induced inhibition was only reversed by w...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(93)80405-j
更新日期:1993-10-25 00:00:00
abstract::The concentration of caffeine required to elute wholly single-stranded DNA from benzoylated DEAE-cellulose is proportional to the polynucleotide length. The use of benzoylated DEAE-cellulose chromatography for isolating and sizing single-stranded regions in double-stranded DNA has been examined using a series of hybri...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(88)80003-6
更新日期:1988-02-15 00:00:00
abstract::E. coli GroEL chaperonin monomers, isolated after urea-induced dissociation of GroEL14, undergo cold denaturation below 5 degrees C. Above 5 degrees C, these monomers undergo MgATP-dependent self-assembly. We have demonstrated a conformational transition at 0 degree C induced by interaction of monomeric GroEL with ade...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(93)81528-8
更新日期:1993-06-07 00:00:00
abstract::In higher eukaryotes, nine aminoacyl-tRNA synthetases form a multienzyme complex also comprising the three auxiliary proteins p18, p38 and p43, of apparent molecular masses of 18, 38 and 43 kDa. The function of these proteins, invariably found associated to the synthetase components of the complex, is unknown. In orde...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(96)01005-8
更新日期:1996-10-14 00:00:00
abstract::To better understand the mechanism of intracellular Ca2+ mobilization, mouse oocytes were micro-injected with 'caged'-inositol-1,4,5 triphosphate caged-InsP3) together with the Ca2+ indicator Fluo-3 to directly induce and monitor Ca2+ redistribution. Photo-released InsP3 elicits [Ca2+]i changes exhibiting several kine...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(90)81474-3
更新日期:1990-11-26 00:00:00
abstract::PsbV2 is a c-type cytochrome present in a very low abundance in the thermophilic cyanobacterium Thermosynechococcus elongatus. We purified this cytochrome and solved its crystal structure at a resolution of 1.5Å. The protein existed as a dimer in the crystal, and has an overall structure similar to other c-type cytoch...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/j.febslet.2013.08.023
更新日期:2013-10-01 00:00:00
abstract::Cyclic AMP-mediated phosphorylation of calcium channel subunits was studied in vitro and in vivo in preparations from dog heart. Calcium channels in native cardiac membranes were phosphorylated by cAMP-dependent protein kinase (PKA) solubilized with digitonin and subsequently immunoprecipitated using a polyclonal anti...
journal_title:FEBS letters
pub_type: 杂志文章
doi:10.1016/0014-5793(93)80733-b
更新日期:1993-12-06 00:00:00