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Abstract: This paper describes the conditions under which autoimmune T cells enter the central nervous system to attack the local tissue. During a prodromal period preceding the onset of neurological disease, the CNS tissue is converted from its physiological immune-hostile state to an immune-friendly state. At the same time, in the peripheral immune system, activated autoimmune T cells undergo profound changes that allow them to enter through the blood-brain barrier and to finally interact with local autoantigen-presenting cells. Antigen recognition leads to T cell activation and the secretion of inflammatory mediators that are responsible for the development of the inflammatory lesions and the neurological deficits. To cite this article: H. Wekerle, C. R. Biologies 330 (2007). [Copyright &y& Elsevier]

Abstract: Akt (PKB) plays a central role in the regulation of cellular antiapoptosis and, thus, is a core intracellular survival factor underlying various human neoplastic diseases. Hence, Akt specific inhibitors create an attractive target for anticancer therapy. We have previously demonstrated that proteins of the TCL1 family (a protooncogene underlying human T cell prolymphocytic leukemia) interact with Akt and functions as Akt kinase coactivators. TCL1 coactivate Akt by binding to its pleckstrin homology domain (Akt-PHD). Then, with the aim to develop an Akt kinase inhibitor, we have hypothesized and verified that a peptide, which spans the Akt binding site (the A β-strand of human TCL1), binds to Akt and modulates Akt kinase activity and its downstream biological responses. Nuclear magnetic studies suggested that Akt_in shares a similar binding site with TCL1, but causes remote conformational changes on the variable loop 1 of the PH domain, the locus mediating phosphoinositide binding. In the present paper, we used NMR titration experiments to demonstrate that the binding of Akt-in to Akt-PHD significantly decreases the affinity of the PH domain for IP4, the sugar headgroup of phosphatidyl-inositol phosphate lipids, responsible for the membrane anchorage of the kinase and its subsequent activation. To cite this article: V. Ropars et al., C. R. Chimie 9 (2006) . [Copyright &y& Elsevier]