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 November 29, 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 November 29, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rural India's Low-Cost Sanitary Pad Revolution

Rural India's Low-Cost Sanitary Pad Revolution

AFP (Nov. 28, 2014) — One man hopes his invention -– a machine that produces cheap sanitary pads –- will help empower Indian women. Duration: 01:51 Video provided by AFP
Powered by NewsLook.com
Research on Bats Could Help Develop Drugs Against Ebola

Research on Bats Could Help Develop Drugs Against Ebola

AFP (Nov. 28, 2014) — In Africa's only biosafety level 4 laboratory, scientists have been carrying out experiments on bats to understand how virus like Ebola are being transmitted, and how some of them resist to it. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
WHO Says Male Ebola Survivors Should Abstain From Sex

WHO Says Male Ebola Survivors Should Abstain From Sex

Newsy (Nov. 28, 2014) — WHO cites four studies that say Ebola can still be detected in semen up to 82 days after the onset of symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
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