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Review
. 2017 Sep 5;7(16):3933-3947.
doi: 10.7150/thno.21529. eCollection 2017.

Nucleic Acid-Based Theranostics for Tackling Alzheimer's Disease

Madhuri Chakravarthy  1   2 , Suxiang Chen  1   2 , Peter R Dodd  3 , Rakesh N Veedu  1   2   3
Affiliations
Review

Nucleic Acid-Based Theranostics for Tackling Alzheimer's Disease

Madhuri Chakravarthy et al. Theranostics. .

Abstract

Nucleic acid-based technologies have received significant interest in recent years as novel theranostic strategies for various diseases. The approval by the United States Food and Drug Administration (FDA) of Nusinersen, an antisense oligonucleotide drug, for the treatment of spinal muscular dystrophy highlights the potential of nucleic acids to treat neurological diseases, including Alzheimer's disease (AD). AD is a devastating neurodegenerative disease characterized by progressive impairment of cognitive function and behavior. It is the most common form of dementia; it affects more than 20% of people over 65 years of age and leads to death 7-15 years after diagnosis. Intervention with novel agents addressing the underlying molecular causes is critical. Here we provide a comprehensive review on recent developments in nucleic acid-based theranostic strategies to diagnose and treat AD.

Keywords: Alzheimer's disease; amyloid beta peptides; chemically modified oligonucleotides; nucleic acid therapeutics.; nucleic acids; tau peptide.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Non-amyloidogenic and amyloidogenic pathways in AD neurons. In the amyloidogenic pathway the APP is aberrantly spliced by BACE1 and γ-secretase to overproduce toxic Aβ species.
Figure 2
Figure 2
The roles of tau in normal neurons and of hyperphosphorylation in AD neurons that lead to neuronal toxicity.
Figure 3
Figure 3
Nucleic acid-based therapeutic strategies. mRNA: messenger RNA; RNase H: ribonuclease H; siRNA: small interfering RNA; RISC: RNA inducing silencing complex; AO: antisense oligonucleotide; antimiR: anti-microRNA; miRNA mimic: microRNA mimic
Figure 4
Figure 4
Examples of chemically-modified nucleotide analogues. 2'-OMe: 2'-O-methyl; 2'-MOE:2'-O-methoxyethyl; 2'-F: 2'-fluoro; 2'-NH2: 2'-amino; FANA: fluoroarabinonucleotide; LNA: locked nucleic acid; TNA: threose nucleic acid; PNA: peptide nucleic acid; PMO: phosphorodiamidate morpholino oligomer; MNA: morpholino nucleic acid; HNA: hexitol nucleic acid; CeNA: cyclohexenyl nucleic acid; ANA: anhydrohexitol nucleic acid
See this image and copyright information in PMC

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