Salmona M

References (7)

Title : Huprine-tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer's and prion diseases - Galdeano_2012_J.Med.Chem_55_661
Author(s) : Galdeano C , Viayna E , Sola I , Formosa X , Camps P , Badia A , Clos MV , Relat J , Ratia M , Bartolini M , Mancini F , Andrisano V , Salmona M , Minguillon C , Gonzalez-Munoz GC , Rodriguez-Franco MI , Bidon-Chanal A , Luque FJ , Munoz-Torrero D
Ref : Journal of Medicinal Chemistry , 55 :661 , 2012
Abstract : A family of huprine-tacrine heterodimers has been developed to simultaneously block the active and peripheral sites of acetylcholinesterase (AChE). Their dual site binding for AChE, supported by kinetic and molecular modeling studies, results in a highly potent inhibition of the catalytic activity of human AChE and, more importantly, in the in vitro neutralization of the pathological chaperoning effect of AChE toward the aggregation of both the beta-amyloid peptide (Abeta) and a prion peptide with a key role in the aggregation of the prion protein. Huprine-tacrine heterodimers take on added value in that they display a potent in vitro inhibitory activity toward human butyrylcholinesterase, self-induced Abeta aggregation, and beta-secretase. Finally, they are able to cross the blood-brain barrier, as predicted in an artificial membrane model assay and demonstrated in ex vivo experiments with OF1 mice, reaching their multiple biological targets in the central nervous system. Overall, these compounds are promising lead compounds for the treatment of Alzheimer's and prion diseases.
ESTHER : Galdeano_2012_J.Med.Chem_55_661
PubMedSearch : Galdeano_2012_J.Med.Chem_55_661
PubMedID: 22185619

Title : Acetylcholinesterase as an amyloid enhancing factor in PrP82-146 aggregation process - Pera_2009_Mol.Cell.Neurosci_40_217
Author(s) : Pera M , Martinez-Otero A , Colombo L , Salmona M , Ruiz-Molina D , Badia A , Clos MV
Ref : Molecular & Cellular Neurosciences , 40 :217 , 2009
Abstract : Acetylcholinesterase (AChE) triggers beta amyloid plaques formation and is associated with amyloid plaques in the brain. Recent studies have demonstrated that AChE promotes the aggregation of PrP106-126, a peptide deduced from the prion protein sequence. In the present study we show that AChE triggers also the fibrillization of the main component of the amyloid plaques -the peptide spanning residues 82-146 (PrP82-146)- found in patients with Gerstmann-Straussler-Scheinker disease (GSS). The kinetics of PrP82-146 aggregate formation was directly correlated with AChE concentration and mature fibrils showed the tinctorial and optical properties of amyloid. Atomic force microscopy analysis showed that oligomer and amyloid fibril formation were significantly accelerated by AChE. This effect was mediated by the peripheral site of the enzyme since propidium iodide inhibited the fibrillization process. Present results strongly support the role of AChE in triggering amyloidogenesis and the potential therapeutic relevance of peripheral site blocker compounds.
ESTHER : Pera_2009_Mol.Cell.Neurosci_40_217
PubMedSearch : Pera_2009_Mol.Cell.Neurosci_40_217
PubMedID: 19038345

Title : Acetylcholinesterase triggers the aggregation of PrP 106-126 - Pera_2006_Biochem.Biophys.Res.Commun_346_89
Author(s) : Pera M , Roman S , Ratia M , Camps P , Munoz-Torrero D , Colombo L , Manzoni C , Salmona M , Badia A , Clos MV
Ref : Biochemical & Biophysical Research Communications , 346 :89 , 2006
Abstract : Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-beta-protein (Abeta) fibril formation in vitro. The presence of prion protein (PrP) in Alzheimer's disease (AD) senile plaques prompted us to assess if AChE could trigger the PrP peptides aggregation as well. Consequently, the efficacy of AChE on the PrP peptide spanning-residues 106-126 aggregation containing a coumarin fluorescence probe (coumarin-PrP 106-126) was studied. Kinetics of coumarin-PrP 106-126 aggregation showed a significant increase of maximum size of aggregates (MSA), which was dependent on AChE concentration. AChE-PrP 106-126 aggregates showed the tinctorial and optical amyloid properties as determined by polarized light and electronic microscopy analysis. A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Abeta aggregation through a similar mechanism. Huprines (AChE inhibitors) also significantly decreased MSA induced by AChE as well, unveiling the potential interest for some AChE inhibitors as a novel class of potential anti-prion drugs.
ESTHER : Pera_2006_Biochem.Biophys.Res.Commun_346_89
PubMedSearch : Pera_2006_Biochem.Biophys.Res.Commun_346_89
PubMedID: 16750169

Title : Effect of acetylcholinesterase inhibitors on AChE-induced PrP106-126 aggregation - Clos_2006_J.Mol.Neurosci_30_89
Author(s) : Clos MV , Pera M , Ratia M , Roman S , Camps P , Munoz-Torrero D , Colombo L , Salmona M , Badia A
Ref : Journal of Molecular Neuroscience , 30 :89 , 2006
Abstract : Transmissible spongiform encephalopaties are caused by an extracellular surface protein, the scrapie prion protein (PrPsc), which is an aberrant form of normal and functional cellular PrP (PrPc). The pathological hallmarks of these diseases are the accumulation and deposition of PrPsc in the form of amyloid fibrils in the central nervous system (Tateishi et al., 1988), similar to amyloid-beta (Abeta) protein in Alzheimer's disease (AD). In some patients, Abeta and prion pathology can coexist (Hainfellner et al., 1998), and a common spatial pattern of protein deposition has been described (Armstrong et al., 2001). In addition, it is well-known that acetylcholinesterase (AChE) colocalizes with Abeta deposits of brains in AD patients and accelerates assembly of Abeta peptides through the peripheral site of the enzyme (Inestrosa et al., 1996). The aim of the present study was to analyze time course and concentration dependence of the AChE proaggregating effect on synthetic peptide-spanning residues 106-126 of human PrP (PrP106-126) and the reversion of this effect by different AChE inhibitors (AChEIs).
ESTHER : Clos_2006_J.Mol.Neurosci_30_89
PubMedSearch : Clos_2006_J.Mol.Neurosci_30_89
PubMedID: 17192641

Title : Intact human lymphocyte membranes respond to muscarinic receptor stimulation by oxotremorine with marked changes in microviscosity and an increase in cyclic GMP - Masturzo_1985_FEBS.Lett_192_194
Author(s) : Masturzo P , Salmona M , Nordstrom O , Consolo S , Ladinsky H
Ref : FEBS Letters , 192 :194 , 1985
Abstract : The muscarinic agonist oxotremorine produced a linear dose-dependent increase in membrane fluidity of intact and viable human lymphocytes in vitro. This effect proved to be receptor-mediated because preincubation with 10(-5)M atropine shifted the dose-response curve one order of magnitude rightward. Pirenzepine preincubation did not affect membrane fluidity variation. A cGMP increase was also found after oxotremorine treatment. The results are discussed in terms of possible modulation of guanyl cyclase and adenyl cyclase through membrane fluidity variations.
ESTHER : Masturzo_1985_FEBS.Lett_192_194
PubMedSearch : Masturzo_1985_FEBS.Lett_192_194
PubMedID: 2998866

Title : Evaluation of epichlorohydrin (ECH) genotoxicity. Microsomal epoxide hydrolase-dependent deactivation of ECH mutagenicity in Schizosaccharomyces pombe in vitro - Rossi_1983_Mutat.Res_109_41
Author(s) : Rossi AM , Migliore L , Loprieno N , Romano M , Salmona M
Ref : Mutat Res , 109 :41 , 1983
Abstract : The mutagenic effect of epichlorohydrin (ECH) on the yeast Schizosaccharomyces pombe was studied in vitro in the presence of mouse-liver S9 mix and microsomal and cytosolic fractions. The incubations were always performed in the absence of NADPH-generating systems. S9 mix and microsomes from phenobarbital-pretreated mice significantly reduced ECH mutagenicity, whereas the cytosol did not result in any deactivating effect. The various protein contents of the subcellular fractions were not involved in any scavenger effect as regards ECH mutagenic activity. Moreover, the addition of reduced glutathione to the incubation mixtures indicated that it did not play an important role, either per se or through the enzyme(s) glutathione-S-epoxide transferase(s), in preventing ECH genotoxicity. Our results suggest that microsomal epoxide hydrolase(s) represents the major step in the detoxifying pathway of ECH. These observations were supported by measurements of the specific epoxide hydrolase activity in the various fractions on the same substrate.
ESTHER : Rossi_1983_Mutat.Res_109_41
PubMedSearch : Rossi_1983_Mutat.Res_109_41
PubMedID: 6835236

Title : Nuclear metabolism. II. Further studies on epoxide hydrolase activity - Gazzotti_1981_Chem.Biol.Interact_35_311
Author(s) : Gazzotti G , Garattini E , Salmona M
Ref : Chemico-Biological Interactions , 35 :311 , 1981
Abstract : Apparent Km- and Vmax-values of nuclear styrene 7,8-oxide hydrolase were determined at different protein concentrations. In the protein concentrations range used no significant differences in the apparent Km-values were observed. The influence of the incubation with different modifiers (i.e. SKF-525A, metyrapone, 1,2-epoxy-3,3,3 trichloropropane, cyclohexene oxide) at two different concentrations on this enzyme activity was also determined. Cyclohexene oxide and 1,2-epoxy-3,3,3-trichloropropane, two well known inhibitors of the microsomal epoxide hydrolase(s) caused a marked inhibition, metyrapone had a strong activating effect whereas SKF-525A had no effect. In vivo pretreatment with phenobarbital significantly induced the nuclear epoxide hydrolase whereas beta-naphthoflavone caused a lower degree of induction. This pattern is quantitatively different but qualitatively very similar to the microsomal one. Moreover a toxifying to detoxifying enzymatic activity balance is attempted for the metabolization of the alkenic double bond of styrene, taking into account the ratio between the styrene monooxygenase (toxifying enzyme) and the styrene, 7,8-oxide hydrolase (detoxifying enzyme) after the above mentioned pretreatments, both in the microsomal and nuclear fractions.
ESTHER : Gazzotti_1981_Chem.Biol.Interact_35_311
PubMedSearch : Gazzotti_1981_Chem.Biol.Interact_35_311
PubMedID: 7226277