Featured Research

from universities, journals, and other organizations

Weak link in Alzheimer's drug candidates: Some may cause further neural degeneration

Date:
April 3, 2010
Source:
University of California - San Diego
Summary:
Some current therapies being investigated for Alzheimer's disease may cause further neural degeneration and cell death, according to a breakthrough discovery.

Ratnesh Lal, a UCSD bioengineering and mechanical engineering professor, led a multi-disciplinary team of researchers in a breakthrough discovery relating to Alzheimer's disease.
Credit: Image courtesy of University of California - San Diego

Some current therapies being investigated for Alzheimer's disease may cause further neural degeneration and cell death, according to a breakthrough discovery by UC San Diego researchers.

By combining three dimensional computer simulations with high resolution atomic force microscopy membrane protein and cell imaging, electrical recording and various cellular assays, UCSD nano-biophysicist Ratnesh Lal and his colleagues investigated the structure and function of truncated peptides, known as nonamyloidgenic peptides, formed by some Alzheimer's drug candidates. The researchers found that the nonamyloidgenic peptides formed active ion channels that caused the cells to take in very high levels of calcium ions, which damaged synaptic efficiency and eventually killed neurons, neurons that are linked to memory loss in human brain.

As a result of their current findings and related previous work, Lal and his colleagues believe that aggregate-forming amyloidogenic peptides promote neurological diseases by forming holes or channels in cell membranes, disturbing ionic homeostasis by allowing unwanted ion flow in-and-out of cells, and most importantly allowing toxic amounts of calcium ions into neural cells. Truncated, shorter non-amyloidogenic peptide fragments that also form ion channels and alter neuronal viability, are assumed by biomedical researchers to be non-toxic and are currently targeted to treat Alzheimer's disease patients. Details of their research were recently published in the Proceedings of the National Academy of Sciences.

"There are several drugs to treat Alzheimer's in Trials I and II, but we don't believe that they will be adopted for clinical usage," said Lal, a joint professor in the UCSD Jacobs School of Engineering's Department of Mechanical and Aerospace Engineering and Bioengineering. We believe we are providing the most direct mechanism of Alzheimer's disease and Down Syndrome pathology. Through our research we have provided a structure and mechanism (an ion channel) that can account for the pathology. The strategy to control the activity of this structure -- the opening and closing of the channel -- should be targeted for an effective treatment."

Lal and his colleagues are now working on a 3D structural model of the ion channel using their data to identify the domains (or sites) of the channel for designing effective therapeutics. Lal said the use of advanced nanotechnology and biology combined with a multi disciplinary approach, aided in the researchers' breakthrough discovery.

"Without advances in technology and a multi disciplinary approach this kind of complex research would not move forward," said Lal, a trained physicist and neurobiologist who joined the UCSD faculty in January 2010 from the University of Chicago.

"My goal is to provide practical solutions for effective human health management using

advances in nanoscience and technology with a multidisciplinary and multi-scale (nano-to-translational) integrated approach," he added.


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hyunbum Jang, Fernando Teran Arce, Srinivasan Ramachandran, Ricardo Capone, Rushana Azimova, Bruce L. Kagan, Ruth Nussinov, and Ratnesh Lal. Truncated β-amyloid peptide channels provide an alternative mechanism for Alzheimer's Disease and Down syndrome. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.0914251107

Cite This Page:

University of California - San Diego. "Weak link in Alzheimer's drug candidates: Some may cause further neural degeneration." ScienceDaily. ScienceDaily, 3 April 2010. <www.sciencedaily.com/releases/2010/04/100401164625.htm>.
University of California - San Diego. (2010, April 3). Weak link in Alzheimer's drug candidates: Some may cause further neural degeneration. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2010/04/100401164625.htm
University of California - San Diego. "Weak link in Alzheimer's drug candidates: Some may cause further neural degeneration." ScienceDaily. www.sciencedaily.com/releases/2010/04/100401164625.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Two US Ebola Patients Leave Hospital Free of the Disease

Two US Ebola Patients Leave Hospital Free of the Disease

AFP (Aug. 21, 2014) Two American missionaries who were sickened with Ebola while working in Liberia and were treated with an experimental drug are doing better and have left the hospital, doctors say on August 21, 2014. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. 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