Down-regulation of amyloid precursor protein by peptide nucleic acid in vivo

Mona Boules, Katrina Williams, Elisa Gollatz, Abdul Fauq, Elliott Richelson

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease associated with increased expression of amyloid precursor protein (APP) and the deposition of its proteolytic cleavage products, the amyloid-β peptides, Aβ 1-40 and Aβ 1-42. Peptide nucleic acids (PNAs) have been shown to block the expression of proteins at transcriptional and translational levels. In this study we used a sense and an antisense PNA specifically targeted to APP to inhibit the transcription and translation of APP by complementary binding to DNA or mRNA, respectively. Using Western blotting, APP showed a drastic decrease (50% and 90% reduction, in two separate experiments, as compared with saline control) with the injection of sense APP. mRNA levels were higher at the same time point after injection of APP sense PNA, most probably because of a compensatory mechanism in response to the drop of APP that might have occurred at an earlier time point (0-1 h) and was reflected in a drop at the protein level at 1 h. The injection of antisense PNA showed about 70% decrease in APP as measured by Western blotting. Unmodified PNA can be used in vivo to reduce the levels of APP, which plays a critical role in the development of AD.

Original languageEnglish (US)
Pages (from-to)123-128
Number of pages6
JournalJournal of Molecular Neuroscience
Volume24
Issue number1
DOIs
StatePublished - Aug 2004

Fingerprint

Peptide Nucleic Acids
Amyloid beta-Protein Precursor
Down-Regulation
Amyloid
Injections
Alzheimer Disease
Western Blotting
Neurodegenerative diseases
Messenger RNA
Protein Binding
Neurodegenerative Diseases
Transcription
Proteins
DNA

Keywords

  • Alzheimer's disease
  • Antisense
  • Peptide nucleic acid
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

Down-regulation of amyloid precursor protein by peptide nucleic acid in vivo. / Boules, Mona; Williams, Katrina; Gollatz, Elisa; Fauq, Abdul; Richelson, Elliott.

In: Journal of Molecular Neuroscience, Vol. 24, No. 1, 08.2004, p. 123-128.

Research output: Contribution to journalArticle

Boules, M, Williams, K, Gollatz, E, Fauq, A & Richelson, E 2004, 'Down-regulation of amyloid precursor protein by peptide nucleic acid in vivo', Journal of Molecular Neuroscience, vol. 24, no. 1, pp. 123-128. https://doi.org/10.1385/JMN:24:1:123
Boules, Mona ; Williams, Katrina ; Gollatz, Elisa ; Fauq, Abdul ; Richelson, Elliott. / Down-regulation of amyloid precursor protein by peptide nucleic acid in vivo. In: Journal of Molecular Neuroscience. 2004 ; Vol. 24, No. 1. pp. 123-128.
@article{391cbfe6cde949dda304b778a0665678,
title = "Down-regulation of amyloid precursor protein by peptide nucleic acid in vivo",
abstract = "Alzheimer's disease (AD) is a neurodegenerative disease associated with increased expression of amyloid precursor protein (APP) and the deposition of its proteolytic cleavage products, the amyloid-β peptides, Aβ 1-40 and Aβ 1-42. Peptide nucleic acids (PNAs) have been shown to block the expression of proteins at transcriptional and translational levels. In this study we used a sense and an antisense PNA specifically targeted to APP to inhibit the transcription and translation of APP by complementary binding to DNA or mRNA, respectively. Using Western blotting, APP showed a drastic decrease (50{\%} and 90{\%} reduction, in two separate experiments, as compared with saline control) with the injection of sense APP. mRNA levels were higher at the same time point after injection of APP sense PNA, most probably because of a compensatory mechanism in response to the drop of APP that might have occurred at an earlier time point (0-1 h) and was reflected in a drop at the protein level at 1 h. The injection of antisense PNA showed about 70{\%} decrease in APP as measured by Western blotting. Unmodified PNA can be used in vivo to reduce the levels of APP, which plays a critical role in the development of AD.",
keywords = "Alzheimer's disease, Antisense, Peptide nucleic acid, Rat",
author = "Mona Boules and Katrina Williams and Elisa Gollatz and Abdul Fauq and Elliott Richelson",
year = "2004",
month = "8",
doi = "10.1385/JMN:24:1:123",
language = "English (US)",
volume = "24",
pages = "123--128",
journal = "Journal of Molecular Neuroscience",
issn = "0895-8696",
publisher = "Humana Press",
number = "1",

}

TY - JOUR

T1 - Down-regulation of amyloid precursor protein by peptide nucleic acid in vivo

AU - Boules, Mona

AU - Williams, Katrina

AU - Gollatz, Elisa

AU - Fauq, Abdul

AU - Richelson, Elliott

PY - 2004/8

Y1 - 2004/8

N2 - Alzheimer's disease (AD) is a neurodegenerative disease associated with increased expression of amyloid precursor protein (APP) and the deposition of its proteolytic cleavage products, the amyloid-β peptides, Aβ 1-40 and Aβ 1-42. Peptide nucleic acids (PNAs) have been shown to block the expression of proteins at transcriptional and translational levels. In this study we used a sense and an antisense PNA specifically targeted to APP to inhibit the transcription and translation of APP by complementary binding to DNA or mRNA, respectively. Using Western blotting, APP showed a drastic decrease (50% and 90% reduction, in two separate experiments, as compared with saline control) with the injection of sense APP. mRNA levels were higher at the same time point after injection of APP sense PNA, most probably because of a compensatory mechanism in response to the drop of APP that might have occurred at an earlier time point (0-1 h) and was reflected in a drop at the protein level at 1 h. The injection of antisense PNA showed about 70% decrease in APP as measured by Western blotting. Unmodified PNA can be used in vivo to reduce the levels of APP, which plays a critical role in the development of AD.

AB - Alzheimer's disease (AD) is a neurodegenerative disease associated with increased expression of amyloid precursor protein (APP) and the deposition of its proteolytic cleavage products, the amyloid-β peptides, Aβ 1-40 and Aβ 1-42. Peptide nucleic acids (PNAs) have been shown to block the expression of proteins at transcriptional and translational levels. In this study we used a sense and an antisense PNA specifically targeted to APP to inhibit the transcription and translation of APP by complementary binding to DNA or mRNA, respectively. Using Western blotting, APP showed a drastic decrease (50% and 90% reduction, in two separate experiments, as compared with saline control) with the injection of sense APP. mRNA levels were higher at the same time point after injection of APP sense PNA, most probably because of a compensatory mechanism in response to the drop of APP that might have occurred at an earlier time point (0-1 h) and was reflected in a drop at the protein level at 1 h. The injection of antisense PNA showed about 70% decrease in APP as measured by Western blotting. Unmodified PNA can be used in vivo to reduce the levels of APP, which plays a critical role in the development of AD.

KW - Alzheimer's disease

KW - Antisense

KW - Peptide nucleic acid

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=16544393156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16544393156&partnerID=8YFLogxK

U2 - 10.1385/JMN:24:1:123

DO - 10.1385/JMN:24:1:123

M3 - Article

VL - 24

SP - 123

EP - 128

JO - Journal of Molecular Neuroscience

JF - Journal of Molecular Neuroscience

SN - 0895-8696

IS - 1

ER -