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- Title
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
- 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 β-amyloid (Aβ) 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 Aβ 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 over-expression of DYRK1A in DS may play a role in accelerating AD pathogenesis through phosphorylation of APP.
- Subjects
PHOSPHORYLATION; AMYLOID; DOWN syndrome; ALZHEIMER'S disease; AMINO acids
- Publication
Journal of Neurochemistry, 2008, Vol 104, Issue 5, p1333
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2007.05075.x