Skip to main content

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Journal of Neuroscience
  • Log in
  • My Cart
Journal of Neuroscience

Advanced Search

Submit a Manuscript
  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE
PreviousNext
Featured ArticleArticles, Neurobiology of Disease

Direct Transcriptional Effects of Apolipoprotein E

Veena Theendakara, Clare A. Peters-Libeu, Patricia Spilman, Karen S. Poksay, Dale E. Bredesen and Rammohan V. Rao
Journal of Neuroscience 20 January 2016, 36 (3) 685-700; DOI: https://doi.org/10.1523/JNEUROSCI.3562-15.2016
Veena Theendakara
1Buck Institute for Research on Aging, Novato, California 94945, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clare A. Peters-Libeu
1Buck Institute for Research on Aging, Novato, California 94945, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patricia Spilman
1Buck Institute for Research on Aging, Novato, California 94945, and
2Easton Laboratories for Neurodegenerative Disease Research, University of California Los Angeles, Los Angeles, California 90025
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Patricia Spilman
Karen S. Poksay
1Buck Institute for Research on Aging, Novato, California 94945, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dale E. Bredesen
1Buck Institute for Research on Aging, Novato, California 94945, and
2Easton Laboratories for Neurodegenerative Disease Research, University of California Los Angeles, Los Angeles, California 90025
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rammohan V. Rao
1Buck Institute for Research on Aging, Novato, California 94945, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

A major unanswered question in biology and medicine is the mechanism by which the product of the apolipoprotein E ε4 allele, the lipid-binding protein apolipoprotein E4 (ApoE4), plays a pivotal role in processes as disparate as Alzheimer's disease (AD; in which it is the single most important genetic risk factor), atherosclerotic cardiovascular disease, Lewy body dementia, hominid evolution, and inflammation. Using a combination of neural cell lines, skin fibroblasts from AD patients, and ApoE targeted replacement mouse brains, we show in the present report that ApoE4 undergoes nuclear translocation, binds double-stranded DNA with high affinity (low nanomolar), and functions as a transcription factor. Using chromatin immunoprecipitation and high-throughput DNA sequencing, our results indicate that the ApoE4 DNA binding sites include ∼1700 gene promoter regions. The genes associated with these promoters provide new insight into the mechanism by which AD risk is conferred by ApoE4, because they include genes associated with trophic support, programmed cell death, microtubule disassembly, synaptic function, aging, and insulin resistance, all processes that have been implicated in AD pathogenesis.

SIGNIFICANCE STATEMENT This study shows for the first time that apolipoprotein E4 binds DNA with high affinity and that its binding sites include 1700 promoter regions that include genes associated with neurotrophins, programmed cell death, synaptic function, sirtuins and aging, and insulin resistance, all processes that have been implicated in Alzheimer's disease pathogenesis.

  • activity-dependent neuroprotective protein
  • Alzheimer's disease
  • amyloid precursor protein
  • apolipoprotein E
  • MAP kinase-activating death domain
  • sirtuin
View Full Text
Back to top

In this issue

The Journal of Neuroscience: 36 (3)
Journal of Neuroscience
Vol. 36, Issue 3
20 Jan 2016
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Advertising (PDF)
  • Ed Board (PDF)
Email

Thank you for sharing this Journal of Neuroscience article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Direct Transcriptional Effects of Apolipoprotein E
(Your Name) has forwarded a page to you from Journal of Neuroscience
(Your Name) thought you would be interested in this article in Journal of Neuroscience.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
Direct Transcriptional Effects of Apolipoprotein E
Veena Theendakara, Clare A. Peters-Libeu, Patricia Spilman, Karen S. Poksay, Dale E. Bredesen, Rammohan V. Rao
Journal of Neuroscience 20 January 2016, 36 (3) 685-700; DOI: 10.1523/JNEUROSCI.3562-15.2016

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Request Permissions
Share
Direct Transcriptional Effects of Apolipoprotein E
Veena Theendakara, Clare A. Peters-Libeu, Patricia Spilman, Karen S. Poksay, Dale E. Bredesen, Rammohan V. Rao
Journal of Neuroscience 20 January 2016, 36 (3) 685-700; DOI: 10.1523/JNEUROSCI.3562-15.2016
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Keywords

  • activity-dependent neuroprotective protein
  • Alzheimer's disease
  • amyloid precursor protein
  • apolipoprotein E
  • MAP kinase-activating death domain
  • sirtuin

Responses to this article

Respond to this article

Jump to comment:

  • Changes in transcription for enzyme responsible for androgen production
    Cheryl A Dyer
    Published on: 31 January 2016
  • Published on: (31 January 2016)
    Page navigation anchor for Changes in transcription for enzyme responsible for androgen production
    Changes in transcription for enzyme responsible for androgen production
    • Cheryl A Dyer, Scientist

    Read your article with great interest. Long ago as a grad student I stumbled on apo E and apo E synthetic peptides suppressing the mRNA for CYP17, the enzyme responsible for producing androgen by ovarian theca and interstitial cells (J Lipid Res. 1998 Dec;39(12):2406-14. An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17alpha-hydrox...

    Show More

    Read your article with great interest. Long ago as a grad student I stumbled on apo E and apo E synthetic peptides suppressing the mRNA for CYP17, the enzyme responsible for producing androgen by ovarian theca and interstitial cells (J Lipid Res. 1998 Dec;39(12):2406-14. An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17alpha-hydroxylase, C17-20 lyase.). Ever since I have struggled to understand how apo E could access DNA, your work appears to finally provide exciting insight. Thank you, one mystery in my apo E research has had a door cracked opened.

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.

Related Articles

Cited By...

More in this TOC Section

Articles

  • Choice Behavior Guided by Learned, But Not Innate, Taste Aversion Recruits the Orbitofrontal Cortex
  • Maturation of Spontaneous Firing Properties after Hearing Onset in Rat Auditory Nerve Fibers: Spontaneous Rates, Refractoriness, and Interfiber Correlations
  • Insulin Treatment Prevents Neuroinflammation and Neuronal Injury with Restored Neurobehavioral Function in Models of HIV/AIDS Neurodegeneration
Show more Articles

Neurobiology of Disease

  • The role of retinal dopamine D1 receptors in ocular growth and myopia development in mice
  • ALS-associated KIF5A mutation causes locomotor deficits associated with cytoplasmic inclusions, alterations of neuromuscular junctions and motor neuron loss
  • Perturbed Information Processing Complexity in Experimental Epilepsy
Show more Neurobiology of Disease
  • Home
  • Alerts
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Issue Archive
  • Collections

Information

  • For Authors
  • For Advertisers
  • For the Media
  • For Subscribers

About

  • About the Journal
  • Editorial Board
  • Privacy Policy
  • Contact
(JNeurosci logo)
(SfN logo)

Copyright © 2023 by the Society for Neuroscience.
JNeurosci Online ISSN: 1529-2401

The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in JNeurosci.