alexa Apolipoprotein E4 induces neuronal cell death under conditions of suppressed de novo cholesterol synthesis.
Psychiatry

Psychiatry

Journal of Addiction Research & Therapy

Author(s): Michikawa M, Yanagisawa K

Abstract Share this page

Abstract The presence of the apolipoprotein E (apoE) allele epsilon4 is a major risk factor for the development of Alzheimer's disease (AD); however, the molecular mechanism underlying the acceleration of AD development in individuals with epsilon4 remains to be determined. To investigate the isoform-specific effects of apoE on neurons, primary neuron cultures were prepared from fetal rat cerebral cortices. Inhibition by compactin, a 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor of de novo cholesterol synthesis, induced premature neuronal cell death in a dose-dependent manner. In the presence of compactin at a sublethal dose to the cells, rabbit beta-migrating very low density lipoprotein (beta-VLDL) with human apoE4 (the product of epsilon4) induced premature neuronal cell death, while that with apoE3 (the product of epsilon3) did not. Neurons cultured in the presence of apoE4, beta-VLDL, and compactin were shrunken and spherical, containing condensed chromatin and fragmented DNA, features characteristic of apoptosis. The addition of intermediate metabolites of the cholesterol biosynthetic pathway, including mevalonate and squalene, rescued neuronal cells incubated with apoE4 and beta-VLDL, in the presence of compactin. These results strongly suggest that a reduction in the level of endogenously synthesized cholesterol is a prerequisite for apoE4-induced neuronal cell death. This article was published in J Neurosci Res and referenced in Journal of Addiction Research & Therapy

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords