Poor recycling of BACE1 enzyme could promote Alzheimer's disease

November 21, 2011 in Medical research

Poor recycling of BACE1 enzyme could promote Alzheimer's disease

Enlarge

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.

More information: Wen, L., et al. 2011. J. Cell Biol. dx.doi.org/10.1083… cb.201105109

Journal reference: Journal of Cell Biology search and more info website

Provided by Rockefeller University search and more info website

not rated yet  

Rank not rated yet
Relevant PhysicsForums posts

More news stories

Study reveals active site of enzyme linked to stuttering

(Medical Xpress)—Scientists from the Joint Center for Structural Genomics (JCSG) at SLAC National Accelerator Laboratory have determined the 3-D structure of the chemically active part of an enzyme involved ...

Medical research created 26 minutes ago | popularity not rated yet | comments 0 | with audio podcast

Researchers develop sperm-sorting design that may aid couples undergoing in vitro fertilization

(Medical Xpress)—According to the World Health Organization, approximately 70 million couples experience infertility worldwide. Current data suggests that nearly one third of infertility disorders are due ...

Medical research created 1 hour ago | popularity 5 / 5 (1) | comments 0

Baby's life saved with groundbreaking 3-D printed device that restored his breathing

Every day, their baby stopped breathing, his collapsed bronchus blocking the crucial flow of air to his lungs. April and Bryan Gionfriddo watched helplessly, just praying that somehow the dire predictions ...

Medical research created 16 hours ago | popularity 5 / 5 (3) | comments 0

Research shows how immune system peacefully co-exists with 'good' bacteria

The human gut is loaded with commensal bacteria – "good" microbes that, among other functions, help the body digest food. The gastrointestinal tract contains literally trillions of such cells, and yet the ...

Medical research created 20 hours ago | popularity 5 / 5 (3) | comments 0 | with audio podcast

Slowing the aging process—only with antibiotics

Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.

Medical research created 20 hours ago | popularity 4.9 / 5 (11) | comments 1 | with audio podcast


Cold plasma successful against brain cancer cells

For the first time, physicists from the Max Planck Institute for Extraterrestrial Physics (MPE), biologists and physicians demonstrated the synergistic effect of cold atmospheric plasma - a partly ionized ...

Can you put a price on health?

As health services strive to improve quality and reduce costs, researchers study the benefits – and the pitfalls – of 'pay for performance' in hospitals.

Are kids who take music lessons different from other kids?

(Medical Xpress)—Research by U of T Mississauga psychology professor Glenn Schellenberg reveals that two key personality traits – openness-to-experience and conscientiousness—predict better than IQ ...

Key find for early bladder cancer treatment

Aggressive forms of bladder cancer involve the protein PODXL – a discovery that could hold the key to improved treatment, according to researchers at Lund University, Uppsala University and KTH in Sweden.

Common brain processes of anesthetic-induced unconsciousness identified

A study from the June issue of Anesthesiology found feedback from the front region of the brain is a crucial building block for consciousness and that its disruption is associated with unconsciousness when the anesthetics ketami ...

Parents can help preteens with abduction concerns

Parents naturally are concerned for their children's safety, particularly when there is news of a child abduction that happens close to home. Finding the balance between emotions and the "teachable moment" as parents talk ...