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Issue title: Tau and Beyond for Alzheimer's Disease: A Special Issue dedicated to Dr. Inge Grundke-Iqbal
Guest editors: Alejandra Alonso and Chengxin Gong
Article type: Research Article
Authors: Qian, Weia; b | Jin, Nanaa; c | Shi, Jianhuab | Yin, Xiaominb | Jin, Xiaoxiaa | Wang, Shibaoa | Cao, Maohongd; e | Iqbal, Khalidc | Gong, Cheng-Xina; c | Liu, Feia; c; *
Affiliations: [a] Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu, China | [b] Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China | [c] Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA | [d] Department of Neurology, Hospital Affiliated to Nantong University, Nantong, Jiangsu, China | [e] The Institute of Neurology, Hospital Affiliated to Nantong University, Nantong, Jiangsu, China
Correspondence: [*] Correspondence to: Fei Liu, Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. Tel.: +1 718 494 4820; Fax: +1 718 494 1080; E-mail: feiliu63@hotmail.com.
Abstract: Microtubule-associated protein tau is found to be accumulated and aggregated in the brains of individuals with Alzheimer's disease and related tauopathies. Dual-specificity tyrosine-phosphorylation regulated kinase 1A (Dyrk1A) is overexpressed in Down syndrome and may play a critical role in the early onset of tau pathology in this disease. To investigate the effect of Dyrk1A on tau expression, we co-expressed different isoforms of tau with Dyrk1A in HEK-293FT cells and measured the mRNA and protein levels of tau using RT-PCR and Western blots, respectively. We further investigated the mechanism of regulation of tau expression by Dyrk1A. We found that Dyrk1A enhanced tau expression in a dose-dependent manner. The enhancement did not require the kinase activity of Dyrk1A. Dyrk1A increased the expression of tau isoforms containing exon 10 to a larger extent than isoforms lacking exon 10. The expression of endogenous tau in neuronal cells was also regulated by Dyrk1A, and increased tau levels were found in the brains of Ts65Dn mice that overexpress Dyrk1A due to partial trisomy of chromosome 16. Dyrk1A did not enhance tau gene transcription, but increased tau mRNA stability. These results suggest that Dyrk1A enhances tau expression by stabilizing its mRNA and provides a novel insight into the regulation of tau expression and a molecular mechanism of tauopathies.
Keywords: Alzheimer's disease, Down syndrome, Dyrk1A, mRNA stability, tau
DOI: 10.3233/JAD-130824
Journal: Journal of Alzheimer's Disease, vol. 37, no. 3, pp. 529-538, 2013
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