Regulation of neuronal APL-1 expression by cholesterol starvation.

PloS One
Mary WieseHui Zheng

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques composed primarily of the amyloid-β peptide, a cleavage product of amyloid precursor protein (APP). While mutations in APP lead to the development of Familial Alzheimer's Disease (FAD), sporadic AD has only one clear genetic modifier: the ε4 allele of the apolipoprotein E (ApoE) gene. Cholesterol starvation in Caenorhabditis elegans leads to molting and arrest phenotypes similar to loss-of-function mutants of the APP ortholog, apl-1 (amyloid precursor-like protein 1), and lrp-1 (lipoprotein receptor-related protein 1), suggesting a potential interaction between apl-1 and cholesterol metabolism. Previously, we found that RNAi knock-down of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. Here we find the same defect is recapitulated during lrp-1 knock-down and by cholesterol starvation. A cholesterol-free diet or loss of lrp-1 directly affects APL-1 levels as both lead to loss of APL-1::GFP fluorescence in neurons. However, loss of cholesterol does not affect global transcription or protein levels as seen by qPCR and Western blot. Our results show that cholesterol and lrp-1 are involved...Continue Reading

References

Jun 10, 1988·Science·C Kenyon
May 1, 1974·Genetics·S Brenner
Dec 5, 1974·Journal of Molecular Biology·H F EpsteinS Brenner
May 17, 1968·Science·W F Hieb, M Rothstein
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·A SaitoM G Farquhar
Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·W J StrittmatterA D Roses
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·K G MillerJ B Rand
Jul 13, 2000·Cellular and Molecular Life Sciences : CMLS·G I Owen, A Zelent
Sep 6, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·M AsahinaS Hirose
Mar 29, 2001·Trends in Genetics : TIG·A E Sluder, C V Maina
Aug 2, 2003·Nature Cell Biology·Teymuras V Kurzchalia, Samuel Ward
Oct 8, 2004·Proceedings of the National Academy of Sciences of the United States of America·Anastasia P GrigorenkoEvgeny I Rogaev
Aug 27, 2005·PLoS Biology·Alison R FrandGary Ruvkun
Jan 2, 2007·Molecular and Cellular Endocrinology·Aarti N UrsMarion B Sewer
Feb 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Angela HornstenChris Li
Dec 1, 2007·WormBook : the Online Review of C. Elegans Biology·Adam Antebi
Oct 3, 2009·The Journal of Cell Biology·Stacey L EdwardsKenneth G Miller

❮ Previous
Next ❯

Datasets Mentioned

BETA
AA1504

Methods Mentioned

BETA
Fluorescence
PCR
protein assay

Software Mentioned

ImageJ
7000 System SDS
Axiovision

Related Concepts

Related Feeds

Allergies & Environmental Factors

Environmental factors are strongly associated with the prevalence of allergies and are an increasing health concern worldwide. Discover the latest research on Allergies and Environmental Factors here.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Alzheimer's Disease: Transcription

Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and AD.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's disease here.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.