P2‐275: Computational and experimental elucidation of Amyloid‐Beta oligomerization and its biological effects

the microarray analysis, we surveyed the binding sites of transcription factors, using the database produced by UCSC Genome Bioinformatics. Results: The increase in the DNA-binding activity of NF-kappa B and AP-1 after exposure to Abeta fibrils was suppressed by PARP-1 inhibitor, 1,5-dihydroxyisoquinoline (DHIQ), and also PARP-1 siRNA. The microarray analysis demonstrated that among 31,042 probes used, 345 and 224 probe sets showed up-regulation and down-regulation, respectively, in the astrocytes after exposure to Abeta fibrils. Furthermore, 87 probe sets showed down-regulation, while only three probe sets showed up-regulation, after addition of DHIQ. Upstream and downstream of the genes detected by these probe sets, the DNA-binding sites of other transcription factors than NF-kappa B and AP-1 were identified. Conclusions: PARP-1 plays an important role in the change of gene expression profile of astrocytes after exposure to A beta fibrils through the activation of a variety of transcription factors. By regulation of these factors, PARP-1 inhibitors could be new therapeutic and/or neuroprotective agents for Alzheimer’s disease.