The IC50 is more than of magnitude higher than that required for CHK1 inhibition

These data suggest that an increase in specific lipid-signaling pathways are able to enhance memory formation during the consolidation period, and together PB 203580 indicate that increased levels of anandamide or its derivatives are able to enhance memory formation. Proper functioning of the nervous system requires functional connections between neurons. This requires undifferentiated neurons to extend neurites that will subsequently differentiate in axons and dendrites to wire the adult brain. Studying the complex morphogenetic event of neurite outgrowth is not only important for understanding the development of the nervous system, but also tissue regeneration after nerve injury and the treatment of neuropathological conditions. Until now most of the work on neurite outgrowth at the cell biology level has been done using R428 routine 2-dimensional culture systems. However, in vivo, cells interact with complex 3-dimensional anisotropic environments that display a different topology from the isotropic 2D environment. In this context, multiple ECM proteins are capable of forming large structures with different geometrical and size features ranging from tens of nanometers to micrometers. The highly organized structure of the ECM is essential for cell and tissue morphogenesis and remodeling. By example, parallel bundles of collagen fibrils are found in connective tissues and laminins assemble basement membrane structures. Laminin tracks on the surface of Schwann cells are also important for neurite outgrowth and neuronal regeneration after a lesion. In this case, laminin most likely assembles fibrillar structures. Furthermore, in the developing nervous system, axons often follow ECM tracks that are oriented along structures such a blood vessels. It is therefore reasonable to assume that precise topological features of the ECM are important for the cell��s ability to interact with and perceive its environment. However, the importance of the ECM organization and topography at the micro- and nano-meter scale is still poorly understood. With recent technological advances in microfabrication, this now becomes accessible. Multiple reports document that the processes of cell migration or of the extension of neuronal processes from neurons are highly dependent on the geometrical topology of the surrounding ECM. Neurons have been reported to respond to different ECM topologies in terms of morphology. When laminin is presented on aligned nanofiber scaffolds, neuronal processes can orient along these fibers compared to randomly oriented scaffolds. Similar alignment behavior has also been observed when neurons are plated on micrometric laminin lines.

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