Featured Research

from universities, journals, and other organizations

Enzyme Is Key To Hallmark Of Alzheimer's -- Moves To Block It Underway

Date:
February 27, 2001
Source:
Johns Hopkins Medical Institutions
Summary:
Scientists at Johns Hopkins have shown that a specific enzyme in the brain is essential for nerve cells to form a hallmark of Alzheimer's disease (AD) — the so-called amyloid plaques that collect and surround brain cells. While aging brains of apparently healthy people contain scattered amyloid plaques, the brains of AD patients are littered with them.

Scientists at Johns Hopkins have shown that a specific enzyme in the brain is essential for nerve cells to form a hallmark of Alzheimer's disease (AD) — the so-called amyloid plaques that collect and surround brain cells. While aging brains of apparently healthy people contain scattered amyloid plaques, the brains of AD patients are littered with them.

Related Articles


Understanding this keystone position of the enzyme beta-secretase marks a significant research step, the scientists say, because blocking the enzyme offers an obvious and — initial studies suggest — a safe target for therapy.

The research is published in the March edition of the journal Nature Neuroscience. It is funded by grants from the National Institute on Aging, Bristol-Myers Squibb Foundation and the Adler Foundation.

"Blocking beta-secretase could have the same effect in people at risk for AD as the vaccines that already are known to keep plaque from forming in tests on lab animals," says lead neuroscientist Philip Wong, Ph.D. "While no research directly links plaque buildup to human AD, blocking plaque does lessen signs of the disease in these animals," Wong says.

"The brain chemistry involved here is virtually identical in mice and humans," says team researcher David Borschelt, Ph.D.

In 1999, five research groups cloned genes for various forms of beta-secretase, but the Hopkins scientists are the first to show that one form of the enzyme (called BACE 1) is key in producing the molecules — within the brain's nerve cells — that become plaque.

In their mouse study, scientists knocked out the gene for their form of beta-secretase. They then cultured nerve cells from the animals' brains and, using antibodies targeted to beta-secretase, confirmed the enzyme wasn't present. Significantly, the Hopkins scientists showed the nerve cells lacking the enzyme failed to form beta amyloid, the plaque protein.

The researchers are also following live mice lacking the gene. "The mice without beta-secretase genes are born apparently normal and seem to suffer no untoward effects, but we're watching them as they age," says Huaibin Cai, Ph.D., another of the researchers. "So far, at eight months, the adult mice appear fine."

"We're really encouraged by possible therapeutic implications," says Wong. "Scientists are already screening for compounds that block the action of beta-secretase in hopes of designing small molecules able to cross the brain's blood-brain barrier." The molecules could, in theory, be fine-tuned to inhibit beta-secretase, Wong adds, which would squelch plaque production. "If that proves therapeutic," he says, "physicians might ultimately give AD patients a "cocktail" of various enzyme-blockers or blockers along with vaccines. "Both approaches may prove useful in treating Alzheimer's," Wong explains.

Beta-secretase works by trimming pieces off a larger molecule that's parent to the plaque protein, beta amyloid. Forming amyloid is a natural cell process, says Wong. It's part of a poorly understood event in cells in which amyloid appears and then is cleared. "But in Alzheimer's," he explains, "something goes wrong and amyloid really increases."

A current hypothesis of AD is that as amyloid builds up, nerve cells are damaged and brain tissues become inflamed. Some researchers believe this chronic inflammation progressively injures nerve cells, leading to the symptoms of the disease.

Scientists say another enzyme, called gamma-secretase, is also involved in brain production of plaque. However, the Hopkins researchers say, the nature of gamma-secretase remains controversial, as does the usefulness of blocking it.

Gamma-secretase is a research hot spot because nearly a quarter of the people with early-onset Alzheimer's have mutations in genes (presenilin genes) linked with the enzyme's activity.

Other members of the research team were Yanshu Wang, Ph.D., Diane McCarthy, Ph.D., Hongjin Wen, M.S. and Donald L. Price, M.D.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Enzyme Is Key To Hallmark Of Alzheimer's -- Moves To Block It Underway." ScienceDaily. ScienceDaily, 27 February 2001. <www.sciencedaily.com/releases/2001/02/010227073721.htm>.
Johns Hopkins Medical Institutions. (2001, February 27). Enzyme Is Key To Hallmark Of Alzheimer's -- Moves To Block It Underway. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2001/02/010227073721.htm
Johns Hopkins Medical Institutions. "Enzyme Is Key To Hallmark Of Alzheimer's -- Moves To Block It Underway." ScienceDaily. www.sciencedaily.com/releases/2001/02/010227073721.htm (accessed October 24, 2014).

Share This



More Mind & Brain News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Academic Scandal Shocks UNC

Academic Scandal Shocks UNC

AP (Oct. 23, 2014) A scandal involving bogus classes and inflated grades at the University of North Carolina was bigger than previously reported, a new investigation found. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Working Mother Getaway: Beaches Turks & Caicos

Working Mother Getaway: Beaches Turks & Caicos

Working Mother (Oct. 22, 2014) Feast your eyes on this gorgeous family-friendly resort. Video provided by Working Mother
Powered by NewsLook.com
What Your Favorite Color Says About You

What Your Favorite Color Says About You

Buzz60 (Oct. 22, 2014) We all have one color we love to wear, and believe it or not, your color preference may reveal some of your character traits. In celebration of National Color Day, Krystin Goodwin (@kyrstingoodwin) highlights what your favorite colors may say about you. Video provided by Buzz60
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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