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Molecular Neurodegeneration

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Open Access 01-12-2012 | Research article

Adeno-associated virus-mediated brain delivery of 5-lipoxygenase modulates the AD-like phenotype of APP mice

Authors: Jin Chu, Phillip F Giannopoulos, Carolina Ceballos-Diaz, Todd E Golde, Domenico Pratico

Published in: Molecular Neurodegeneration | Issue 1/2012

Abstract

Background

The 5-lipoxygenase (5LO) enzymatic pathway is widely distributed within the central nervous system. Previous works showed that this protein is up-regulated in Alzheimer's disease (AD), and that its genetic absence results in a reduction of Amyloid beta (Aβ) levels in the Tg2576 mice.

Here by employing an adeno-associated viral (AAV) vector system to over-express 5LO in the same mouse model, we examined its contribution to their cognitive impairments and brain AD-like amyloid pathology.

Results

Our results showed that compared with controls, 5LO-targeted gene brain over-expression in Tg2576 mice results in significant memory deficits. On the other hand, brain tissues had a significant elevation in the levels of Aβ peptides and deposition, no change in the steady state levels of amyloid-β precursor protein (APP), BACE-1 or ADAM-10, but a significant increase in PS1, nicastrin, and Pen-2, three major components of the γ-secretase complex. Additional data indicate that the transcription factor CREB was elevated and so were the mRNA levels for PS1, nicastrin and Pen-2.

Conclusions

These data demonstrate that neuronal 5LO plays a functional role in the pathogenesis of AD-like amyloidotic phenotype by modulating the γ-secretase pathway. They support the hypothesis that this enzyme is a novel therapeutic target for the treatment and prevention of AD.

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Title: Adeno-associated virus-mediated brain delivery of 5-lipoxygenase modulates the AD-like phenotype of APP mice
Authors: Jin Chu
Phillip F Giannopoulos
Carolina Ceballos-Diaz
Todd E Golde
Domenico Pratico
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2012
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-7-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Adeno-associated virus-mediated brain delivery of 5-lipoxygenase modulates the AD-like phenotype of APP mice

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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