Diametric shift in 2 protein levels spurs Alzheimer's plaque accumulation

A diametric shift in the levels of two proteins involved in folding, moving and cutting other proteins enables accumulation of the destructive brain plaque found in Alzheimer's disease, researchers report.

VPS35 is a protein that folds others into specific positions to unleash their functions. When levels are reduced as they are in aging, it unleashes the normally dormant BACE1, a protein responsible for beta production, Georgia Health Sciences University researchers report in The .

When researchers modified a mouse model of Alzheimer's so that VPS35 production was essentially cut in half, BACE1 activity was increased, accelerating aging and development of related problems such as and poor communication between as well as beta amyloid accumulation, said Dr. Wen-Cheng Xiong, developmental and Weiss Research Professor at GHSU and the study's corresponding author.

It was known that expression of VPS35 was down and BACE1 was up in Alzheimer's but the direct relationship was unknown, Xiong said. "We believe impaired function of VPS35 could be a risk factor for Alzheimer's and Parkinson's diseases," Xiong said. Discovering the relationship makes VPS35 a potential biomarker for the diseases as well as a target for new therapies to keep VPS35 elevated. The accelerated aging model Xiong developed and patented will enable these future drug studies.

This unhealthy balance causes cells to accumulate more waste than their recycling systems can handle. Additionally misfolded proteins end up in the wrong cell compartment where they form aggregates that eventually kill the cell. Being in the wrong place is what enables BACE1 activity to increase: it ends up stuck in a cell compartment called the where high activate the protein. As BACE1 becomes more numerous and active, it chops up more potentially productive proteins, turning them into garbage.

"Each protein knows its destination, lifespan and when it should be degraded; everything is controlled. With aging, their trafficking, their control system is disrupted," Xiong said.

Future questions include what reduces VPS35 levels, such as increased levels of reactive oxygen species that come with age, and whether exercise can help keep them up. 'We think VPS35 will be a new, hot and hopefully productive area for Alzheimer's and Parkinson's research," Xiong said.

The protein is classified a retromer. Retromers are important to recycling inside cells. While silent in healthy adults, BACE1 plays an important role in brain development.

Related Stories

Genetic mutation linked to Parkinson's disease

date Jul 15, 2011

Researchers have discovered a new gene mutation they say causes Parkinson's disease. The mutation was identified in a large Swiss family with Parkinson's disease, using advanced DNA sequencing technology.

Recommended for you

Organ transplant rejection may not be permanent

date 13 hours ago

Rejection of transplanted organs in hosts that were previously tolerant may not be permanent, report scientists from the University of Chicago. Using a mouse model of cardiac transplantation, they found that immune tolerance ...

Researchers find key mechanism that causes neuropathic pain

date 15 hours ago

Scientists at the University of California, Davis, have identified a key mechanism in neuropathic pain. The discovery could eventually benefit millions of patients with chronic pain from trauma, diabetes, shingles, multiple ...

Deep sea light shines on drug delivery potential

date 15 hours ago

A naturally occurring bioluminescent protein found in deep sea shrimp—which helps the crustacean spit a glowing cloud at predators—has been touted as a game-changer in terms of monitoring the way drugs ...

User comments

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

Click here to reset your password.
Sign in to get notified via email when new comments are made.