Featured Research

from universities, journals, and other organizations

Tackling cognitive deficits in Alzheimer's disease: One 'STEP' at a time

Date:
October 18, 2010
Source:
Yale University
Summary:
Lowering levels of a key protein involved in regulating learning and memory -- STtriatal-Enriched tyrosine Phosphatase (STEP) -- reversed cognitive deficits in mice with Alzheimer's disease, researchers report.

Lowering levels of a key protein involved in regulating learning and memory -- STtriatal-Enriched tyrosine Phosphatase (STEP) -- reversed cognitive deficits in mice with Alzheimer's disease, Yale School of Medicine researchers report in the October 18 issue of Proceedings of the National Academy of Sciences.

Related Articles


"This finding provides a rationale for drug discovery and for developing therapeutic agents that could inhibit STEP proteins and might improve the outlook for Alzheimer's disease patients," said senior author of the study Paul Lombroso, M.D., professor in the Yale Child Study Center and in the Departments of Neurobiology and Psychiatry at Yale School of Medicine.

To test the idea that lowering STEP levels might reverse cognitive deficit in Alzheimer's disease, Lombroso and a team that included Nobel laureate Paul Greengard of Rockefeller University conducted a study on mice that were genetically engineered to still have the Alzheimer's mutation, but without the STEP protein. They compared these animals to mice with only the Alzheimer's mutation in a series of memory tests including a water maze. Mice without the STEP protein learned the maze after a 10-day training period, but the Alzheimer's mice did not. "This tells us that reducing STEP levels is sufficient to reverse the cognitive defect in these mice," said Lombroso.

Lombroso discovered the STEP protein in earlier studies. Past research has shown that increased STEP levels are caused by the toxic peptide beta amyloid that blocks an organelle programmed to destroy these proteins. "When that organelle is inhibited, proteins, including STEP won't be degraded and will accumulate," said Lombroso.

Lombroso said that glutamate receptors on the surface of neurons are key to learning and memory. He and his team determined that the excess level of STEP was removing these glutamate receptors and preventing short-term memories from turning into long-term memories.

In addition to Alzheimer's disease, increased levels of STEP in the brain have been implicated in other disorders such as schizophrenia and Fragile X, which is characterized by cognitive deficits and other disabilities. Once again, high levels of STEP proteins remove glutamate receptors from synapses and contribute to the cognitive deficits present in these diseases.

"These new findings need to be replicated, but if genetically reducing STEP levels is improving cognition, we could perhaps discover a drug designed to reduce STEP activity," said Lombroso. "Our current work is focused on looking for STEP inhibitors."

The study was funded by the American Health Assistance Foundation.

Other authors on the study include Yongfang Zhang, Pradeep Kurup, Jian Xu, Nikisha Carty, Stephanie Fernandez, Haakon B. Nygaard, Christopher Pittenger, Stephen M. Strittmatter and Angus C. Nairn.


Story Source:

The above story is based on materials provided by Yale University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yongfang Zhang, Pradeep Kurup, Jian Xu, Nikisha Carty, Stephanie M. Fernandez, Haakon B. Nygaard, Christopher Pittenger, Paul Greengard, Stephen M. Strittmatter, Angus C. Nairn, Paul J. Lombroso. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1013543107

Cite This Page:

Yale University. "Tackling cognitive deficits in Alzheimer's disease: One 'STEP' at a time." ScienceDaily. ScienceDaily, 18 October 2010. <www.sciencedaily.com/releases/2010/10/101018162924.htm>.
Yale University. (2010, October 18). Tackling cognitive deficits in Alzheimer's disease: One 'STEP' at a time. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2010/10/101018162924.htm
Yale University. "Tackling cognitive deficits in Alzheimer's disease: One 'STEP' at a time." ScienceDaily. www.sciencedaily.com/releases/2010/10/101018162924.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
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