Affiliations: [a] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, CO, USA | [b] Department of Pharmacology, University of Colorado Denver School of Medicine, Aurora, CO, USA
Correspondence:
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Corresponding author: Les A. Krushel, University of Colorado School of Medicine, Department of Biochemistry and Molecular Genetics, P.O. Box 6511, Mail Stop 8101, Aurora, CO 80045, USA. Tel.: +1 303 724 3646; Fax: +1 303 724 3221; E-mail: Leslie.Krushel@ucdenver.edu.
Abstract: Neurofibrillary tangles are a pathological phenotype in Alzheimer's disease (AD) and are caused by the hyperphosphorylation of the microtubule associated protein tau. In mouse models of AD, decreasing tau protein expression limits the severity of symptoms and inhibits progression of AD. We now report that the 5' leader in the human tau mRNA contains an internal ribosomal entry site (IRES) and that IRES-dependent translation plays a role in the synthesis of tau protein. Consequently, targeting the tau IRES provides a novel target for regulating tau expression in AD and other tauopathies.
Keywords: Alzheimer's disease, internal ribosomal entry site, protein synthesis, tauopathy
