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
- 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
- Author
- 서혜명
- Keywords
- Alzheimer's disease; APP; beta-amyloid; Down syndrome; DYRK1A; phosphorylation
- Issue Date
- 2008-03
- Publisher
- BLACKWELL PUBLISHING
- Citation
- JOURNAL OF NEUROCHEMISTRY, v. 104, No. 5, Page. 1333-1344
- 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.
- URI
- https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2007.05075.xhttps://repository.hanyang.ac.kr/handle/20.500.11754/107190
- ISSN
- 0022-3042
- DOI
- 10.1111/j.1471-4159.2007.05075.x
- Appears in Collections:
- COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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