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Current Drug Targets for Modulating Alzheimer's Amyloid Precursor Protein: Role of Specific Micro-RNA Species

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Alzheimer's disease (AD) is the most common form of dementia in the United States and is increasing in prevalence every year throughout the world. Recent clinical trial failures highlight the need for further insights into the molecular events that underlie the neurobiology of AD. Pathological aberrations in AD are believed to result, in part, from excess accumulation of amyloid-beta peptide (Aβ), a product of Aβ precursor protein (APP). Targeting APP levels would then be expected to reduce Aβ production in all forms of AD. Therefore, clarifying the regulatory network that governs APP expression is likely to reveal molecular players that could serve as novel drug targets. This review highlights recent work demonstrating the involvement of microRNA (miRNA) in this regulatory network. MiRNA are small, non-coding RNA that interact with target mRNA at sites of imperfect complementarity and mediate translational inhibition or transcript destabilization. We first review the neurobiology of AD and describe current therapeutic strategies. We then review transcriptional and post-transcriptional mechanisms utilized by cells to control APP expression. We conclude by highlighting recent work, including our own, which suggests miRNA are integral components of this regulatory framework and potential targets for future AD therapeutics.

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Keywords: APP expression; Aging; Amyloid; Brain disorders; CNS; Dementia; Drug target; MicroRNA-101; Neurodegeneration; Neuronal; Non-coding RNA; Post-transcriptional

Document Type: Research Article

Publication date: 2011-08-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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