UMMS Affiliation

Department of Medicine; Program in Neuroscience; Program in Gene Function and Expression

Publication Date

1-6-2009

Document Type

Article

Subjects

Alternative Splicing; Alzheimer Disease; Animals; Dementia; Exons; Humans; Mutation; Oligoribonucleotides, Antisense; Tauopathies; tau Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Tau aggregation is one of the major features in Alzheimer's disease and in several other tauopathies, including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), and progressive supranuclear palsy (PSP). More than 35 mutations in the tau gene have been identified from FTDP-17 patients. A group of these mutations alters splicing of exon 10, resulting in an increase in exon 10 inclusion into tau mRNA. Abnormal splicing with inclusion of exon 10 into tau mRNA has also been observed in PSP and AD patients. These results indicate that abnormal splicing of exon 10, leading to the production of tau with exon 10, is probably one of the mechanisms by which tau accumulates and aggregates in tauopathic brains. Therefore, modulation of exon 10 splicing in the tau gene could potentially be targeted to prevent tauopathies. To identify small molecules or compounds that could potentially be developed into drugs to treat tauopathies, we established a cell-based high-throughput screening assay. In this review, we will discuss how realistic, specific biological molecules can be found to regulate exon 10 splicing in the tau gene for potential treatment of tauopathies.

Rights and Permissions

Citation: BMC Neurosci. 2008 Dec 3;9 Suppl 2:S10. Link to article on publisher's site

DOI of Published Version

10.1186/1471-2202-9-S2-S10

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

BMC neuroscience

PubMed ID

19090983

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