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P2‐275: Computational and experimental elucidation of Amyloid‐Beta oligomerization and its biological effects
Author(s) -
Teplow David
Publication year - 2011
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.2011.05.1154
Subject(s) - random hexamer , function (biology) , amyloid beta , molecular dynamics , beta (programming language) , computational biology , chemistry , monomer , biophysics , computer science , peptide , biology , biochemistry , microbiology and biotechnology , computational chemistry , programming language , organic chemistry , polymer
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.