5 research outputs found
How the nature of the compounds present in solid and liquid compartments of activated sludge impact its rheological characteristics
A novel DYRK1A (Dual specificity tyrosine phosphorylationâregulated kinase 1A) inhibitor for the treatment of Alzheimer's disease: effect on Tau and amyloid pathologies in vitro
International audienceThe dualâspecificity tyrosine phosphorylationâregulated kinase 1A (DYRK1A) gene is located within the Down Syndrome (DS) critical region on chromosome 21 and is implicated in the generation of Tau and amyloid pathologies that are associated with the early onset Alzheimer's Disease (AD) observed in DS. DYRK1A is also found associated with neurofibrillary tangles in sporadic AD and phosphorylates key AD players (Tau, amyloid precursor, protein, etc). Thus, DYRK1A may be an important therapeutic target to modify the course of Tau and amyloid beta (AÎČ) pathologies. Here, we describe EHT 5372 (methyl 9â(2,4âdichlorophenylamino) thiazolo[5,4âf]quinazolineâ2âcarbimidate), a novel, highly potent (IC50 = 0.22 nM) DYRK1A inhibitor with a high degree of selectivity over 339 kinases. Models in which inhibition of DYRK1A by siRNA reduced and DYRK1A overâexpression induced Tau phosphorylation or AÎČ production were used. EHT 5372 inhibits DYRK1Aâinduced Tau phosphorylation at multiple ADârelevant sites in biochemical and cellular assays. EHT 5372 also normalizes both AÎČâinduced Tau phosphorylation and DYRK1Aâstimulated AÎČ production. DYRK1A is thus as a key element of AÎČâmediated Tau hyperphosphorylation, which links Tau and amyloid pathologies. EHT 5372 and other compounds in its class warrant in vivo investigation as a novel, highâpotential therapy for AD and other Tau opathies
Effect and analysis of phenolic compounds during somatic embryogenesis induction in Feijoa sellowiana Berg
Summary. The effect of phenolic compounds on somatic embryogenesis in Feijoa sellowiana was analysed. The results showed that caffeic acid (140â560 ”M) significantly increased somatic embryogenesis induction compared with the control. The presence of phloridzin, even at lower concentrations (11.5 ”M), or caffeic acid or phloroglucinol at concentrations greater than 140.0 and 197.5 ”M, respectively, inhibited somatic embryo development beyond the globular stage. When somatic embryos were transferred to the germination medium, the highest rates of germination (81.9%) were obtained with embryos induced in the presence of phloroglucinol (79.0 ”M). At all concentrations tested, somatic embryos induced in medium containing phloroglucinol germinated at higher rates than those induced in the presence of caffeic acid. Histological and ultrastructural studies showed that somatic embryos were formed in close association with phenolic-rich cells which, in more advanced stages of development, formed a zone isolating the embryo from the maternal tissue. A comparative analysis of total phenolic content indicated that phenolics reached a peak by the third week of culture, independently of the medium used. However, after that period, the amount of phenolic compounds was significantly higher in explants cultured in the presence of phloroglucinol than in those cultured in the control or in caffeic acid-containing medium. Attempts to identify the type of phenolic compounds showed that flavan-3-ols and gallic acid derivatives were mainly produced in phloroglucinol-containing medium, whereas flavanones and dihydroflavonols were also present in medium containing caffeic acid. Flavones were the main phenols detected in the control. The ways in which phenolic compounds may affect somatic embryogenesis are discussed