Poor recycling of BACE1 enzyme could promote Alzheimer's disease

Poor recycling of BACE1 enzyme could promote Alzheimer's disease
A study in the Journal of Cell Biology suggests that sluggish recycling of the BACE1 enzyme could promote Alzheimer's disease. Relative to control cells (left), cells short on the protein VPS35 (right) accumulate more BACE1 (red) in endosomes (green). BACE1 in endosomes appears yellow. Credit: Wen, L., et al. 2011. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201105109

Sluggish recycling of a protein-slicing enzyme could promote Alzheimer's disease, according to a study published online on November 21 in The Journal of Cell Biology.

Abeta, the that accumulates in the brains of Alzheimer's patients, is formed when enzymes cut up its parental protein, known as amyloid . One of those enzymes is beta-secretase or BACE1. BACE1 cycles between the Golgi apparatus and the plasma membrane, traveling through endosomes on the way. A protein complex called the retromer helps back from endosomes to the Golgi. Previous studies have found reduced levels of two retromer components, including the protein VPS35, in the brains of patients with Alzheimer's disease.

To find out whether VPS35 affects Alzheimer's disease progression, Wen-Cheng Xiong and colleagues crossed two mouse lines to create animals that are prone to many symptoms of the disease and generate half the normal amount of VPS35. The mice displayed Alzheimer's-like abnormalities earlier than their parental strains, and their brains accumulated more Abeta.

Cells lacking VPS35 carried extra BACE1 in their endosomes, consistent with a defect in retromer-mediated . BACE1 is more active in the acidic interior of endosomes than in the more basic surroundings of the Golgi apparatus. Thus, by leaving more BACE1 trapped in endosomes, the decline in VPS35 levels could enhance BACE1 activity and generate more Abeta. Although no VPS35 mutations have so far turned up in Alzheimer's patients, the protein's level in the brain dwindles in aging mice. The researchers suspect that certain Alzheimer's disease risk factors, such as oxidative stress, also diminish VPS35 levels in the brain.


Explore further

Key action of a gene linked to both Alzheimer's disease and type 2 diabetes identified

More information: Wen, L., et al. 2011. J. Cell Biol. dx.doi.org/10.1083/jcb.201105109
Provided by Rockefeller University
Citation: Poor recycling of BACE1 enzyme could promote Alzheimer's disease (2011, November 21) retrieved 24 March 2019 from https://medicalxpress.com/news/2011-11-poor-recycling-bace1-enzyme-alzheimer.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
 shares

Feedback to editors

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more