transient receptor potential canonical (TRPC) proteins form Ca (2 +) – permeable cation channel activated on stimulation of metabotropic receptors coupled to phospholipase C. Among the subfamily TRPC, TRPC3 and TRPC6 channel directly activated by diacylglycerol (DAG) plays an important role in < em> brain – derived neurotrophic factor ( BDNF ) signals, promoting the development of neuronal and survival , In various disease models, BDNF to restore neurological deficit, but its therapeutic potential is limited by poor pharmacokinetic profiles.
Explanation framework for designing small molecules, which Stirs BDNF -like activity through TRPC3 and TRPC6, establish a solid basis to overcome these limitations. We found, through the screening of the library, a group of piperazine- derived a compound that activates a DAG-activated TRPC3 / TRPC6 / TRPC7 channels. Compound 4 – (5-chloro-2-methylphenyl) piperazine-1-yl methanone (PPZ1) and 2 – [ 4 – (2 , 3-dimethylphenyl) piperazine-1-yl] -N- (2-ethoxyphenyl) acetamide (PPZ2) is activated, dose-dependent manner, recombinant TRPC3 / TRPC6 / TRPC7 channels, but no other TRPCs, The human embryonic kidney cells. PPZ2 activated TRPC6 as the original channels in smooth muscle cells isolated from rabbit portal vein. Also, PPZ2 generate cation currents and Ca (2+) influx of cultured rat neurons center.
Strikingly, both compounds induced BDNF -like neurite growth and neuroprotection, which was abolished by knockdown or inhibition TRPC3 / TRPC6 / TRPC7 in cultured neurons. Inhibitors of Ca (2+) signaling pathway, except calcineurin, promotion of neurite disruption caused by PPZ compound. PPZ2 increased activation of Ca (2 +) – dependent transcription factor , cAMP response element-binding protein.
These findings indicate that Ca (2+) signaling is mediated by activation of DAG-activated channel underlies TRPC neurotrophic the effect of the compound PPZ. Thus, piperazine- derived TRPC channel activator DAG-activated provide important insights for the future development of a new class of synthetic neurotrophic drug.
Relevance of Post-Stroke Circulating Levels of BDNF as a prognostic biomarker Stroke Outcomes.
Impact of rt-PA treatment. recombinant the form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. More recently, the t-PA has been associated with metabolic brain – derived neurotrophic factor ( BDNF ), the main neurotrophin is involved in post-stroke neuroplasticity.
Thus, the purpose of our study was to investigate the effects of rt-PA treatment of post-stroke circulating BDNF level Human and in animals. Serum BDNF levels and t-PA activity / plasmin was measured at admission and up to 90 days in stroke patients who receive (n = 2 4 ) or not (n = 1 4 ) rt-PA perfusion. We investigated the relationship between serum BDNF with the same t-PA / plasmin activity, the results of neurological and cardiovascular score at admission.
Description: Fully biologically active when compared to standard. Determined by the dose-dependent induction of choline acetyl transferase activity in rat basal forebrain primary septal cell cultures was found to be in the range of 20-50 ng/ml, corresponding to a Specific Activity of ＞2 x 104 IU/mg.
Description: Fully biologically active when compared to standard. Determined by the dose-dependent induction of choline acetyl transferase activity in rat basal forebrain primary septal cell cultures was found to be in the range of 20-50 ng/ml, corresponding to a Specific Activity of ＞2 x 104 IU/mg.
Description: Neurotrophin-3 Human Recombinant produced in E. coli is a non-glycosylated and non-covalently linked homodimer, containing 2x119 amino acid chains, having a total Mw of 27.2 kDa. The NT-3 is purified by proprietary chromatographic techniques.
Description: Quantitativesandwich ELISA kit for measuring Human Neurotrophin 4, NT-4 in samples from serum, plasma, cell culture supernates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Human Neurotrophin 4, NT-4 in samples from serum, plasma, cell culture supernates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
In parallel, serum BDNF levels and t-PA activity / plasmin were assessed before and after (1, 4 and 2 4 h) induced an ischemic stroke in mice. Our study showed higher serum BDNF levels and better neurological outcomes in the rt-PA-treated compared to non-treated patients. However, serum BDNF level does not predict the outcome of a blow when the entire cohort of stroke patients were analyzed.
