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P3–223: Caspase activity is inhibited in neuronal cells infected with Chlamydia pneumoniae: Implications for apoptosis in Alzheimer's disease
Author(s) -
Way Deana S.,
Albert Elizabeth V.,
Hammond Christine J.,
Bell Marcus G.,
Balin Brian J.,
Appelt Denah M.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1492
Subject(s) - staurosporine , apoptosis , biology , caspase , chlamydophila pneumoniae , programmed cell death , microbiology and biotechnology , alzheimer's disease , caspase 3 , microglia , cancer research , chlamydia , immunology , disease , signal transduction , medicine , chlamydiaceae , inflammation , biochemistry , protein kinase c
of A uptake 2) the requirement of A internalization for A -induced toxicity. Methods: Primary neurons cultured in three-compartmented dishes were treated with oligomeric fluorescein-conjugated A 1-42 exclusively in the distal axonor the cell body-containing compartments.A uptake and intracellular transport were analyzed by fluorescent microscopy and/or ELISA.The role of clathrinand caveolamediated endocytosis was analyzed in neurons infected with recombinant adenoviruses expressing HA-tagged wild-type dynamin-1, HA-tagged dynK44A mutant, or T7tagged clathrin hub. Neuronal apoptosis was determined by nuclear fragmentation and caspase activation. Results: A 1-42 was internalized mainly through the distal axons and retrogradely transported to cell bodies. Conversely, neurons treated with A 1-42 exclusively in the cell bodies showed very little A 1-42 internalization and anterograde transport . This result suggests that A 1-42 enters the cell by a regulated mechanism. Two main internalization pathways exist: namely clathrinand caveolae-mediated endocytosis. Both mechanisms require dynamin, but only the former is mediated by clathrin. Neurons expressing the dominat negative mutant of dynamin 1, showed a dramatic decrease in A 1-42 transport from distal axons to cell bodies. Conclusions: Our data suggest the oligomeric A 1-42 internalization is independent of clathrin. Our model is relevant to the death of basal forebrain cholinergic neurons in AD.