Pharmacological targeting of α-synuclein and TPPP/p25 in Parkinson's disease: challenges and opportunities in a Nutshell.

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 Lett

journal_title

FEBS letters

authors

Oláh J,Ovádi J

doi

10.1002/1873-3468.13464

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

1641-1653

issue

13

eissn

0014-5793

issn

1873-3468

journal_volume

593

pub_type

杂志文章,评审
  • Inhibition of the mitochondrial cyclosporin A-sensitive permeability transition pore by the arginine reagent phenylglyoxal.

    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

    authors: Eriksson O,Fontaine E,Petronilli V,Bernardi P

    更新日期:1997-06-16 00:00:00

  • Identification of a fetal exon in the human fast troponin T gene.

    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

    authors: Briggs MM,Maready M,Schmidt JM,Schachat F

    更新日期:1994-08-15 00:00:00

  • Photodamaged D1 protein is degraded in Arabidopsis mutants lacking the Deg2 protease.

    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

    authors: Huesgen PF,Schuhmann H,Adamska I

    更新日期:2006-12-22 00:00:00

  • Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases.

    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

    authors: Kostoulas G,Lang A,Nagase H,Baici A

    更新日期:1999-07-23 00:00:00

  • Preference of calcium-dependent interactions between calmodulin-like domains of calpain and calpastatin subdomains.

    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

    authors: Takano E,Ma H,Yang HQ,Maki M,Hatanaka M

    更新日期:1995-03-27 00:00:00

  • A new mutation in the pufL gene responsible for the terbutryn resistance phenotype in Rubrivivax gelatinosus.

    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

    authors: Ouchane S,Picaud M,Astier C

    更新日期:1995-10-23 00:00:00

  • Dual role of tropomyosin on chemically modified actin filaments from skeletal muscle.

    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

    authors: Honda H,Kitano Y,Hatori K,Matsuno K

    更新日期:1996-03-25 00:00:00

  • Tumor suppressor RBM5 directly interacts with the DExD/H-box protein DHX15 and stimulates its helicase activity.

    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

    authors: Niu Z,Jin W,Zhang L,Li X

    更新日期:2012-04-05 00:00:00

  • Diversity and similarity in the tRNA world: overall view and case study on malaria-related tRNAs.

    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

    authors: Pütz J,Giegé R,Florentz C

    更新日期:2010-01-21 00:00:00

  • Effect of truncated glucagon-like peptide 1 on cAMP in rat gastric glands and HGT-1 human gastric cancer cells.

    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

    authors: Hansen AB,Gespach CP,Rosselin GE,Holst JJ

    更新日期:1988-08-15 00:00:00

  • In vivo study of the state of order of the membranes of gram-negative bacteria by Fourier-transform infrared spectroscopy (FT-IR).

    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

    authors: Schultz C,Naumann D

    更新日期:1991-12-02 00:00:00

  • TAK1-mediated transcriptional activation of CD28-responsive element and AP-1-binding site within the IL-2 promoter in Jurkat T cells.

    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

    authors: Sakurai H,Singhirunnusorn P,Shimotabira E,Chino A,Suzuki S,Koizumi K,Saiki I

    更新日期:2005-12-05 00:00:00

  • Preparation and structure of the charge-transfer intermediate of the transmembrane redox catalyst DsbB.

    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

    authors: Malojcić G,Owen RL,Grimshaw JP,Glockshuber R

    更新日期:2008-10-15 00:00:00

  • Suppression of Mycobacterium tuberculosis induced reactive oxygen species (ROS) and TNF-alpha mRNA expression in human monocytes by allicin.

    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

    authors: Hasan N,Yusuf N,Toossi Z,Islam N

    更新日期:2006-05-01 00:00:00

  • Trendspotting in the Protein Data Bank.

    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

    authors: Berman HM,Coimbatore Narayanan B,Di Costanzo L,Dutta S,Ghosh S,Hudson BP,Lawson CL,Peisach E,Prlić A,Rose PW,Shao C,Yang H,Young J,Zardecki C

    更新日期:2013-04-17 00:00:00

  • Balancing presynaptic release and endocytic membrane retrieval at hair cell ribbon synapses.

    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

    authors: Pangrsic T,Vogl C

    更新日期:2018-11-01 00:00:00

  • Induction of caspase-11 by inflammatory stimuli in rat astrocytes: lipopolysaccharide induction through p38 mitogen-activated protein kinase pathway.

    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

    authors: Hur J,Kim SY,Kim H,Cha S,Lee MS,Suk K

    更新日期:2001-10-26 00:00:00

  • Thermodynamic considerations on the formation of reactive species from hypochlorite, superoxide and nitrogen monoxide. Could nitrosyl chloride be produced by neutrophils and macrophages?

    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

    authors: Koppenol WH

    更新日期:1994-06-20 00:00:00

  • A new superfamily of putative NTP-binding domains encoded by genomes of small DNA and RNA viruses.

    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

    authors: Gorbalenya AE,Koonin EV,Wolf YI

    更新日期:1990-03-12 00:00:00

  • Inhibition of glycosphingolipid synthesis induces p34cdc2 activation in Xenopus oocyte.

    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

    authors: De Smedt V,Rime H,Jessus C,Ozon R

    更新日期:1995-11-20 00:00:00

  • 2',3'-Dialdehydo-UDP-N-acetylglucosamine inhibits UDP-N-acetylglucosamine 2-epimerase, the key enzyme of sialic acid biosynthesis.

    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

    authors: Blume A,Chen H,Reutter W,Schmidt RR,Hinderlich S

    更新日期:2002-06-19 00:00:00

  • Selection for TRAIL resistance results in melanoma cells with high proliferative potential.

    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

    authors: Wu JJ,Zhang XD,Gillespie S,Hersey P

    更新日期:2005-03-28 00:00:00

  • Unfolding of bacteriophage P22 tailspike protein: enhanced thermal stability of an N-terminal fusion mutant.

    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

    authors: Carbonell X,Villaverde A

    更新日期:1998-08-07 00:00:00

  • Reversible inactivation of endothelial nitric oxide synthase by NG-nitro-L-arginine.

    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

    authors: Mayer B,Schmid M,Klatt P,Schmidt K

    更新日期:1993-10-25 00:00:00

  • Sizing of single-stranded regions in double-stranded DNA by preparative benzoylated DEAE-cellulose chromatography.

    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

    authors: Norris MD,Stewart BW

    更新日期:1988-02-15 00:00:00

  • Stabilization of a compact conformation of monomeric GroEL at low temperature by adenine nucleotides.

    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

    authors: Lissin NM,Hemmingsen SM

    更新日期:1993-06-07 00:00:00

  • The p18 component of the multisynthetase complex shares a protein motif with the beta and gamma subunits of eukaryotic elongation factor 1.

    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

    authors: Quevillon S,Mirande M

    更新日期:1996-10-14 00:00:00

  • InsP3- and Ca2(+)-induced Ca2+ release in single mouse oocytes.

    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

    authors: Peres A

    更新日期:1990-11-26 00:00:00

  • Crystal structure at 1.5Å resolution of the PsbV2 cytochrome from the cyanobacterium Thermosynechococcus elongatus.

    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

    authors: Suga M,Lai TL,Sugiura M,Shen JR,Boussac A

    更新日期:2013-10-01 00:00:00

  • Phosphorylation of the L-type calcium channel beta subunit is involved in beta-adrenergic signal transduction in canine myocardium.

    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

    authors: Haase H,Karczewski P,Beckert R,Krause EG

    更新日期:1993-12-06 00:00:00