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Sphingosine-1-phosphate (S1P) is a lipid mediator that exerts multiple cellular functions through activation of G-protein-coupled receptors. Although the role of S1P on angiogenesis is well established, its role in neurogenesis is unknown. We examined the effects of S1P on G-protein activation in brain sections of rat embryo and on neural progenitor cells(More)
We studied the role of FGF-2 on regulation of neurogenesis and cell loss in the granule cell layer (GCL) of the hippocampal dentate gyrus after experimental traumatic brain injury (TBI). In both FGF-2(-/-) and FGF-2(+/+) mice subjected to controlled cortical impact, the number of dividing cells labeled with BrdU, injected on posttrauma days 6 through 8,(More)
Signal transducers and activators of transcription (STAT) proteins are a family of transcription factors that play a crucial role in growth and differentiation in a variety of cell types. Among them, STAT1, which is expressed in the brain and directly activated by reactive oxygen species, participates in the regulation of cytokine-signaling and cellular(More)
Cell cycle inhibition of neural stem and progenitor cells is critical for maintaining the stability of central nervous system in adults, but it may represent a significant hurdle for neural regeneration after injury. We have previously demonstrated that the cyclin-dependent kinase inhibitor (CKI) p21(cip1/waf1) (p21) maintains the quiescence of neural(More)
Neural precursor cells from adults have exceptional proliferative and differentiative capability in vitro yet respond minimally to in vivo brain injury due to constraining mechanisms that are poorly defined. We assessed whether cell cycle inhibitors that restrict stem cell populations in other tissues may participate in limiting neural stem cell reactivity(More)
The discovery and optimization of a novel series of FATP1 inhibitors are described. Through the derivatization process, arylpiperazine derivatives 5k and 12a were identified as possessing potent in vitro activity against human and mouse FATP1s as well as excellent pharmacokinetic properties. In vivo evaluation of triglyceride accumulation in the liver,(More)
The discovery, optimization and structure-activity relationship of novel FATP1 inhibitors have been described. The detailed SAR studies of each moiety of the inhibitors combined with metabolite analysis led to the identification of the potent inhibitors 11p and 11q with improved blood stability.
We show an efficient method to identify molecular targets of small molecular compounds by affinity purification and mass spectrometry. Binding proteins were isolated from target cell lysate using affinity columns, which immobilized the active and inactive compounds. All proteins bound to these affinity columns were eluted by digestion using trypsin and then(More)
Both excitotoxicity and apoptosis contribute to neuronal loss in various neurodegenerative diseases such as Alzheimer's disease as well as stroke, and a drug inhibiting both types of cell death may lead to practical treatment for these diseases. Post-treatment with troglitazone, a potent and specific activator of peroxisome proliferator-activated receptor(More)
Mutations of the KRAS or BRAF genes are now recognized as prognostic markers for colorectal cancer (CRC). They are also important predictive markers for resistance to the monoclonal antibodies that target the epidermal growth factor receptor. In this retrospective study, KRAS and BRAF mutations were analyzed using a direct sequence method in 254 Japanese(More)