NF-kB control of neuronal apoptosis in Alzheimer disease

National Institute On Aging

Investigators

Linked publications & trials

Abstract

During fiscal year 2009, we accomplished the following: 1. Determined that Cox-2 activation via the T cell receptor in CD4+ T cells requires the NF-kB component c-Rel. Conversely, Cox-2-deficient CD4+ T cells do not induce c-Rel effectively, with consequent down-regulation of c-Rel inducible genes such as Bcl-XL. These observations indicate the existence of a regulatory circuit whereby c-Rel is essential for Cox-2 expression and Cox-2, in turn, contributes to c-Rel gene induction. 2. We extended our analysis of death receptor-initiated CD4+ T cell death to passive death caused by withdrawal of activating signals. We found that Cox-2 provides anti-apoptotic function against passive cell death and has no effect on death-receptor-induced cell death. 3. We used CD4+T cells from spleen and lymph nodes of conditional Dicer-deficient mice. Generation of functional micro-RNAs is blocked in the absence of Dicer . We found that Dicer-deficiency increased activation-induced cell death in CD4+ T cell blasts from both sources. These observations provide the first indication that micro-RNAs may regulate death-receptor induced cell death of CD4+ T lymphocytes.