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P3‐311: Swedish amyloid precursor protein mutation increases cell cycle‐related proteins in vitro and in vivo
Author(s) -
Choi Yoori,
Ahn Kwang-Woo,
Joo Yuyoung,
Kim Minji,
Lee Sang Hyoung,
Cha Seok-Ho,
Suh Yoo-Hun,
Kim Hye-Sun
Publication year - 2008
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.2008.05.1880
Subject(s) - gsk 3 , amyloid precursor protein , cyclin d1 , neurodegeneration , cell cycle , biology , microbiology and biotechnology , downregulation and upregulation , gsk3b , kinase , chemistry , alzheimer's disease , cell , biochemistry , medicine , gene , disease
NGF. Methods: We used quantitative RT-PCR, Western blot, RNAi, survival assay and immunocytochemistry in this study. Results: We find that SEI-1 transcripts and protein levels are elevated in response to NGF deprivation. Moreover, down-regulation of SEI-1 by RNAi protects neurons from death induced by NGF deprivation. Recently, we reported that Cdk4-mediated Rb phosphorylation leads to de-repression of the E2Fresponsive gene Myb and consequent induction of the apoptotic protein Bim and that these actions are required for neuron death in response to NGF deprivation or -amyloid (A ) exposure. We now find that interference with expression of SEI-1 by siRNAs blocks Rb phosphorylation, Myb expression and Bim induction in response to NGF deprivation. Moreover, our results indicate that SEI-1 is also induced in response to A treatment of cultured cortical neurons. Given the induction of SEI-1 by A exposure and the similarities in the mechanisms of neuron death in response to NGF deprivation and A exposure noted by our and other groups, we anticipate that SEI-1 will also mediate neuron degeneration evoked by A exposure. Conclusions: Our observations indicate that SEI-1 initiates activation of a cell cycle pathway that leads to degeneration of neurons in response to NGF deprivation and A exposure and identify SEI-1 as a potential therapeutic target in AD.