Featured Research

from universities, journals, and other organizations

Brain enzyme is double whammy for Alzheimer's disease

Date:
August 20, 2012
Source:
Sanford-Burnham Medical Research Institute
Summary:
The underlying causes of Alzheimer's disease are not fully understood, but a good deal of evidence points to the accumulation of β-amyloid, a protein that's toxic to nerve cells. β-amyloid -- a toxic protein known to accumulate in the brains of most Alzheimer's disease patients -- is formed by several enzymes, including BACE1. Researchers have now found that BACE1 does more than just help produce β-amyloid -- it also regulates another cellular process that contributes to memory loss. This is important information for drug makers looking to target BACE1 to prevent or treat Alzheimer's disease.

This shows beta-amyloid plaques (red) in the brain of an Alzheimer's disease patient.
Credit: Sanford-Burnham Medical Research Institute

The underlying causes of Alzheimer's disease are not fully understood, but a good deal of evidence points to the accumulation of β-amyloid, a protein that's toxic to nerve cells. β-amyloid is formed by the activity of several enzymes, including one called BACE1. Most Alzheimer's disease patients have elevated levels of BACE1, which in turn leads to more brain-damaging β-amyloid protein. In a paper published August 15 in The Journal of Neuroscience, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) found that BACE1 does more than just help produce β-amyloid -- it also regulates another cellular process that contributes to memory loss. This means that just inhibiting BACE1's enzymatic activity as a means to prevent or treat Alzheimer's disease isn't enough -- researchers will have to prevent cells from making it at all.

"Memory loss is a big problem -- not just in Alzheimer's disease, but also in the normal aging population," said Huaxi Xu, Ph.D., professor in Sanford-Burnham's Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and senior author of the study. "In this study, we wanted to better understand how BACE1 plays a role in memory loss, apart from β-amyloid production."

To do this, Xu and his team used a mouse model that produces human BACE1. Mice produce a different type of β-amyloid, one that's far less toxic than the human version. So, in this system, they could look solely at how BACE1 functions independent from β-amyloid formation. If BACE1 only acted to produce β-amyloid, the researchers would expect to see no effect when mice produce human BACE1 -- since mouse β-amyloid isn't very toxic, extra BACE1 would be no big deal. Instead, they saw that the enzyme still impaired learning and memory, indicating a secondary function at work.

If it's not producing β-amyloid, what is BACE1 doing? Many years ago, scientists found that a protein in the brain -- protein kinase A (PKA), better known for directing cellular metabolism -- also plays an important role in memory formation. In this study, Xu and colleagues found that BACE1 disrupts the cell's production of other molecules required for PKA function. By that mechanism, BACE1 inactivates PKA and therefore inhibits memory formation in mice, even in the absence of neurotoxic β-amyloid.

"So BACE1 is a double whammy when it comes to memory," Xu said. "But that also means that a therapy that targets BACE1 could be a double punch against Alzheimer's disease, and even just normal aging-related memory loss. That's why we're now looking for ways to block BACE1 expression in the brain."


Story Source:

The above story is based on materials provided by Sanford-Burnham Medical Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Y. Chen, X. Huang, Y.-w. Zhang, E. Rockenstein, G. Bu, T. E. Golde, E. Masliah, H. Xu. Alzheimer's -Secretase (BACE1) Regulates the cAMP/PKA/CREB Pathway Independently of -Amyloid. Journal of Neuroscience, 2012; 32 (33): 11390 DOI: 10.1523/JNEUROSCI.0757-12.2012

Cite This Page:

Sanford-Burnham Medical Research Institute. "Brain enzyme is double whammy for Alzheimer's disease." ScienceDaily. ScienceDaily, 20 August 2012. <www.sciencedaily.com/releases/2012/08/120820093753.htm>.
Sanford-Burnham Medical Research Institute. (2012, August 20). Brain enzyme is double whammy for Alzheimer's disease. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2012/08/120820093753.htm
Sanford-Burnham Medical Research Institute. "Brain enzyme is double whammy for Alzheimer's disease." ScienceDaily. www.sciencedaily.com/releases/2012/08/120820093753.htm (accessed September 2, 2014).

Share This




More Mind & Brain News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
Coffee Then Napping: The (New) Key To Alertness

Coffee Then Napping: The (New) Key To Alertness

Newsy (Aug. 30, 2014) Researchers say having a cup of coffee then taking a nap is more effective than a nap or coffee alone. Video provided by Newsy
Powered by NewsLook.com
Young Entrepreneurs Get $100,000, If They Quit School

Young Entrepreneurs Get $100,000, If They Quit School

AFP (Aug. 29, 2014) Twenty college-age students are getting 100,000 dollars from a Silicon Valley leader and a chance to live in San Francisco in order to work on the start-up project of their dreams, but they have to quit school first. Duration: 02:20 Video provided by AFP
Powered by NewsLook.com
Baby Babbling Might Lead To Faster Language Development

Baby Babbling Might Lead To Faster Language Development

Newsy (Aug. 29, 2014) A new study suggests babies develop language skills more quickly if their parents imitate the babies' sounds and expressions and talk to them often. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins