KMID : 0381120160380050479
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Genes and Genomics 2016 Volume.38 No. 5 p.479 ~ p.487
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Effects of sarah/nebula knockdown on A¥â42-induced phenotypes during Drosophila development
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Bang Se-Min
Lee Soo-Jin Jeong Hae-Min Hong Yoon-Ki Lee Jang-Ho Hwang Soo-Jin Suh Yoon-Seok Lee Kyung-Hoon Cho Kyoung-Sang
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Abstract
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The Down syndrome critical region 1 (DSCR1), a Down syndrome-associated protein, is an endogenous inhibitor of the Ca2+-dependent phosphatase calcineurin. It has been also suggested to be associated with Alzheimer¡¯s disease (AD) but the role of DSCR1 in the pathogenesis of AD still remains controversial. In this paper, we investigated the effects of knockdown of sarah (sra), a Drosophila DSCR1 ortholog, on the A¥â42-induced developmental phenotypes of Drosophila. Knockdown of sra showed detrimental effects on the rough eye phenotype and survival of A¥â42-expressing flies without altering the A¥â42 accumulation. Furthermore, the knockdown of sra increased glial cell numbers in the larval brains and its susceptibility to oxidative stress. Overexpression of an active form of calcineurin produced similar results to sra knockdown as they both exacerbated the A¥â42-induced rough eye phenotype. However, sra knockdown did not alter apoptosis or c-Jun N-terminal kinase activation in A¥â42-expressing flies. In conclusion, our results suggest that sra does play an important role in A¥â42-induced developmental defects in Drosophila without affecting its stress responses.
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KEYWORD
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Alzheimer¡¯s disease, Amyloid-¥â-42, Calcineurin, Drosophila, DSCR1/RCAN1, Sarah/nebula
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