• We designed SSOs that block APP exon splicing

  2024-11-01

  

  We designed SSOs that block APP exon 17 splicing and induce the production of an alternatively spliced APP mRNA lacking exon 17 (APPΔex17). APPΔex17 mRNA encodes an APP protein isoform that lacks 49 Cyclic Pifithrin-α hydrobromide including the γ-secretase cleavage sites that give rise to the toxic

• An important observation is that

  2024-10-31

  

  An important observation is that this patient has been on ALK inhibitor for more than 4 years (51 months: 27 months on crizotinib+24 months on alectinib and on-going) and there was no evidence of disease progression in the central nervous system. The other potential driver mutation in this patient’s

• carboxypeptidase DAergic as well as GABAergic and glutamater

  2024-10-31

  

  DAergic, as well as GABAergic and glutamatergic neurons, send projections to target forebrain structures, such as the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), and support diverse functional roles (Carr and Sesack, 2000a, Carr and Sesack, 2000b, Omelchenko and Sesack, 2009, Taylor

• To examine whether the interaction between mGlu and adrenerg

  2024-10-31

  

  To examine whether the interaction between mGlu7 and α1-adrenergic receptors could be confirmed at a behavioural level, we performed the FST in mice. This test has value in predicting the antidepressant-like effect of drugs or environmental manipulations (Krishnan and Nestler, 2008, Krishnan and Nes

• phosphodiesterase inhibitors The results also showed that th

  2024-10-31

  

  The results also showed that the A3 receptor agonist increased the phosphorylated levels of Akt, leading to activation of the PI3K/Akt pathway. A3 phosphodiesterase inhibitors stimulation has protective effects against RGC death following ischemia-reperfusion, glutamate toxicity, and optic nerve tr

• The enzyme mediated ATP sensing mechanism in zebrafish

  2024-10-31

  

  The enzyme-mediated ATP-sensing mechanism in zebrafish can be compared with previous studies in other animal species reporting that enzymatic conversion of chemicals in the peripheral olfactory organ results in either “activation” or “inactivation” of odorants and pheromones. In male silkmoth, the a

• As an alternative to chronic receptor blockade we

  2024-10-31

  

  As an alternative to chronic receptor blockade, we have been targeting adenosine kinase (ADK) – an astrocyte-based enzyme that catalyses the phosphorylation of adenosine, as a means to modify BAMB-4 adenosinergic signalling (Boison, 2006, Etherington et al., 2009). Up-regulating ADK facilitates the

• 7-Nitroindazole synthesis br Introduction Epilepsy is charac

  2024-10-31

  

  Introduction Epilepsy is characterized by spontaneous recurrent seizures and represents one of the most frequent neurological diseases affecting about 60 million people worldwide (McNamara, 1999). It is estimated that up to 50% of all cases are triggered by “initial precipitating injuries”, such

• Both subcutaneous s c and mucosal

  2024-10-31

  

  Both subcutaneous (s.c.) and mucosal administration of short synthetic peptide derivatives of AChR prevent the onset of EAMG, but do not treat ongoing EAMG [80], [81], [82], [83], [84], [85]. The selection of peptides for treatment is mainly based on the identification of immunodominant T- and B-cel

• Additional evidence for a putative role of COXs and

  2024-10-31

  

  Additional evidence for a putative role of COXs and 5-LOX in AD derives from pharmacological studies using inhibitors of these enzymes (for review, see Firuzi and Praticò, 2006). In addition to helping delineate the pathobiological mechanisms of AD, these results raise hope for discovering novel the

• The presence of different LO splice variants

  2024-10-31

  

  The presence of different 5-LO splice variants was first demonstrated in human BAY 11-7082 tumour cells and in dimethyl sulfoxide-differentiated HL-60 cells [40] and a correlation between the 5-LO splicing pattern and the malignancy of the brain tumours was found. Later, other splice variants were i

• Eicosanoids are locally acting signaling lipids that are pro

  2024-10-31

  

  Eicosanoids are locally acting signaling lipids that are produced from C20 polyunsaturated fatty acids (PUFAs), including arachidonic 94535 synthesis (AA, C20:4), eicosapentaenoic acid (C20:5) and eicosatrienoic acid (C20:3) (Dennis and Norris, 2015; Funk, 2001; Stables and Gilroy, 2011). According

• The tumor suppressor function of LOX

  2024-10-31

  

  The tumor-suppressor function of 15-LOX-2 in normal prostate epithelial cells may be explained by the induction of replicative senescence [14,15]. Thus, 15-LOX-2 is overexpressed in age-dependent prostatic hyperplasia, but cell senescence may hinder progression to malignant transformation. Notwithst

• Melphalan Although the LB domains of mGlu receptors

  2024-10-31

  

  Although the LB2 domains of mGlu receptors have not been shown to form an extensive interface during activation, they do draw closer to each other, as demonstrated in crystal structures (Kunishima et al., 2000, Muto et al., 2007, Tsuchiya et al., 2002) and by FRET analysis (Doumazane et al., 2013, V

• l Arginine supplementation was reported to be efficient inef

  2024-10-30

  

  l-Arginine supplementation was reported to be efficient, inefficient or toxic in aged patients. The present study does not support our hypothesis that increased tissue arginase activity may account for the ineffectiveness and even the toxicity of l-arginine supplementation in ageing. Indeed, except

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