Current drug targets for modulating Alzheimer's amyloid precursor protein: Role of specific micro-RNA species

J. M. Long, Debomoy Lahiri

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3314-3321
Number of pages8
JournalCurrent Medicinal Chemistry
Volume18
Issue number22
DOIs
StatePublished - Aug 2011

Fingerprint

Amyloid beta-Protein Precursor
MicroRNAs
Alzheimer Disease
Protein Precursors
Pharmaceutical Preparations
Neurobiology
Small Untranslated RNA
Amyloid beta-Peptides
Aberrations
Dementia
Clinical Trials
Messenger RNA
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Current drug targets for modulating Alzheimer's amyloid precursor protein : Role of specific micro-RNA species. / Long, J. M.; Lahiri, Debomoy.

In: Current Medicinal Chemistry, Vol. 18, No. 22, 08.2011, p. 3314-3321.

Research output: Contribution to journalArticle

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