Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer's disease
- Authors
- Ryoo, Soo-Ryoon; Cho, Hyun-Jeong; Lee, Hye-Won; Jeong, Hey Kyeong; Radnaabazar, Chinzorig; Kim, Yeun-Soo; Kim, Min-Jeong; Son, Mi-Young; Seo, Hyemyung; Chung, Sul-Hee; Song, Woo-Joo
- Issue Date
- Mar-2008
- Publisher
- Blackwell Publishing Inc.
- Keywords
- Alzheimer' s disease; APP; beta-amyloid; Down syndrome; DYRK1A; phosphorylation
- Citation
- Journal of Neurochemistry, v.104, no.5, pp.1333 - 1344
- Indexed
- SCIE
SCOPUS
- Journal Title
- Journal of Neurochemistry
- Volume
- 104
- Number
- 5
- Start Page
- 1333
- End Page
- 1344
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/42616
- DOI
- 10.1111/j.1471-4159.2007.05075.x
- ISSN
- 0022-3042
- Abstract
- Most individuals with Down Syndrome (DS) show an early-onset of Alzheimer's disease ( AD), which potentially results from the presence of an extra copy of a segment of chromosome 21. Located on chromosome 21 are the genes that encode beta-amyloid (A beta) precursor protein (APP), a key protein involved in the pathogenesis of AD, and dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A (DYRK1A), a proline-directed protein kinase that plays a critical role in neurodevelopment. Here, we describe a potential mechanism for the regulation of AD pathology in DS brains by DYRK1A-mediated phosphorylation of APP. We show that APP is phosphorylated at Thr668 by DYRK1A in vitro and in mammalian cells. The amounts of phospho-APP and Ab are increased in the brains of transgenic mice that over-express the human DYRK1A protein. Furthermore, we show that the amounts of phospho-APP as well as those of APP and DYRK1A are elevated in human DS brains. Taken together, these results reveal a potential regulatory link between APP and DYRK1A in DS brains, and suggest that the overexpression of DYRK1A in DS may play a role in accelerating AD pathogenesis through phosphorylation of APP.
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