Targeting mRNA for Alzheimer’s and Related Dementias
Author
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-04-27
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Brain deposition of the amyloid beta-protein (Aβ) and tau are characteristic features in Alzheimer’s disease (AD).
Mutations in the Aβ precursor protein (APP) and a protease involved in Aβ production from APP strongly argue for a pathogenic role of Aβ in AD, while mutations in tau are associated with related disorders collectively called frontotemporal lobar degeneration (FTLD).
Despite intense effort, therapeutic strategies that target Aβ or tau have not yet yielded medications, suggesting that alternative approaches should be pursued.
In recent years, our laboratory has studied the role of mRNA in AD and FTLD, specifically those encoding tau and the Aβ-producing protease BACE1.
As many FTLD-causing tau mutations destabilize a hairpin structure that regulates RNA splicing, we have targeted this structure with small molecules, antisense oligonucleotides, and small molecule-antisense conjugates.
We have also discovered that microRNA interaction with the 3′-untranslated region of tau regulates tau expression.
Regarding BACE1, we found that alternative splicing leads to inactive splice isoforms and antisense oligonucleotides shift splicing toward these inactive isoforms to decrease Aβ production.
In addition, a G-quadruplex structure in the BACE1 mRNA plays a role in splice regulation.
The prospects for targeting tau and BACE1 mRNAs as therapeutic strategies will be discussed.
American Psychological Association (APA)
Wolfe, Michael S.. 2014. Targeting mRNA for Alzheimer’s and Related Dementias. Scientifica،Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-1047588
Modern Language Association (MLA)
Wolfe, Michael S.. Targeting mRNA for Alzheimer’s and Related Dementias. Scientifica No. 2014 (2014), pp.1-13.
https://search.emarefa.net/detail/BIM-1047588
American Medical Association (AMA)
Wolfe, Michael S.. Targeting mRNA for Alzheimer’s and Related Dementias. Scientifica. 2014. Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-1047588
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1047588