Featured Research

from universities, journals, and other organizations

Fatal Protein Interactions May Explain Neurological Diseases

Date:
September 7, 2008
Source:
University of California - San Diego
Summary:
Researchers have investigated how proteins involved in neurodegenerative diseases such as Alzheimer's and Parkinson's disease interact to form unique complexes. Their findings explain why Alzheimer's patients might develop Parkinson's, and vice versa. The new and unique molecular structures they discovered can now be used to model and develop new drugs for these devastating neurological diseases.

Molecular modeling of hybrid ±-syn (alpha-syn) (white) and Abeta (orange) oligomer in plasma membrane of affected neuron.
Credit: UCSD

In a collaborative study at the University of California, San Diego, investigators from neurosciences, chemistry and medicine, as well as the San Diego Supercomputer Center (SDSC) have investigated how proteins involved in neurodegenerative diseases such as Alzheimer's and Parkinson's disease interact to form unique complexes. Their findings explain why Alzheimer's patients might develop Parkinson's, and vice versa.

The new and unique molecular structures they discovered can now be used to model and develop new drugs for these devastating neurological diseases. Their findings will be published in the September 3 issue of Public Library of Science (PLoS) ONE on September 4, 2008.

The team, led by Eliezer Masliah, M.D., professor of neurosciences and pathology in the UC San Diego School of Medicine, found that "fatal" or abnormal interactions among the a-synuclein protein (a-syn, involved in Parkinson's disease) and Abeta amyloid (Aß, which leads to the plaques associated with Alzheimer's disease) interact and form unique "hybrid" complexes. These hybrid abnormal protein interactions result in combined neurodegenerative diseases.

"Clinically, we knew that having one neurological disease, such as Alzheimer's, put patients at risk for another neurological disease in combination with it, for example, Parkinson's disease or frontotemporal dementia. But as doctors and scientists, we didn't understand why this occurred until now," Masliah said. Through computer modeling, they discovered that when the Aß and a-syn interacted they formed a new hybrid protein with a small hole called a "nanopore" that alters neuronal activity. Masliah described the model of the hybrid complex as being "like looking at a boat with holes in it. Because we can now see the holes, we can learn how to stop the leak."

Misfolding and aggregation of neuronal proteins has been proposed to play a critical role in the development of neurodegenerative disorders, including the leading disorders in the aging population – Alzheimer's disease and Parkinson's disease – which result in dementia and movement disorders. More than five million Americans live with such neurological conditions, and it is estimated that this country alone will see a 50 percent increase in Alzheimer's and Parkinson's disease alone by the year 2025.

In Alzheimer's, Aß accumulates in the intracellular and extracellular spaces of the brain, leading to the formation of plaques. In Parkinson's, intracellular accumulation of an abundant synaptic protein, a-syn, results in the formation of characteristic foreign substances called "Lewy bodies." The mechanisms through which Aß and a-syn interactions might lead to additional neurodegeneration have been the subject of intense scientific investigation, according to Masliah.

Working with researchers at the SDSC, Masliah and colleagues, including first author Igor Tsygelni from the Department of Chemistry and Biochemistry, developed a dynamic model using computer simulations. These included the so-called "molecular dynamics process," which allows insight into molecular motion on an atomic scale. Used to determine the properties of complex systems that contain a vast number of particles through use of numerical methods, molecular dynamics allowed the team to model how the abnormal neuronal proteins docked with other proteins or with cell membranes, and to measure the energies of interaction.

"This sort of modeling, to determine the structure of these complexes, was never before possible," said Masliah, adding that it was only possible at UC San Diego with its strong culture of scientific collaboration and the computing power of the San Diego Supercomputer Center. "With this novel technology, we have come to a new understanding of these combined neurological diseases, and have a model for developing new drugs to treat them."

These studies were supported by electron microscopy, along with cell and tissue studies of both mice and human brains, to characterize the nature of the interaction between the two proteins.

Co-investigators on this paper, all at UC San Diego, include first author Igor F. Tsigelny, Department of Chemistry and Biochemistry and the San Diego Supercomputer Center; Jason X.-J. Yuan and Oleksandr Platoshyn, Department of Medicine; Leslie Crews, Department of Pathology; Paula Desplats, Gideon M. Shaked, Hideya Mizuno, Brian Spencer, Edward Rockenstein and Margarita Trejo, Department of Neurosciences; and Yuriy Sharikov, San Diego Supercomputer Center.

The study was funded in part by the National Institutes of Health, IBM under its Institutes of Innovation program as well as computational support on its BlueGene computers at the San Diego Supercomputer Center and at the Argonne National Laboratory.


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.


Cite This Page:

University of California - San Diego. "Fatal Protein Interactions May Explain Neurological Diseases." ScienceDaily. ScienceDaily, 7 September 2008. <www.sciencedaily.com/releases/2008/09/080903204225.htm>.
University of California - San Diego. (2008, September 7). Fatal Protein Interactions May Explain Neurological Diseases. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2008/09/080903204225.htm
University of California - San Diego. "Fatal Protein Interactions May Explain Neurological Diseases." ScienceDaily. www.sciencedaily.com/releases/2008/09/080903204225.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) — The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) — Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) — Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) — Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
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