Featured Research

from universities, journals, and other organizations

New hope for diseases of protein folding such as Alzheimer’s, Parkinson’s diseases, ALS, cancer and diabetes

Date:
January 8, 2012
Source:
Northwestern University
Summary:
Two related studies offer new strategies for tackling the challenges of preventing and treating diseases of protein folding, such as Alzheimer's, Parkinson's and Huntington's diseases, ALS, cystic fibrosis, cancer and type 2 diabetes. The research identifies new genes and pathways that prevent protein misfolding and toxic aggregation, keeping cells healthy, and also identifies small molecules with therapeutic potential that restore health to damaged cells, providing new targets for drug development.

Two related studies from Northwestern University offer new strategies for tackling the challenges of preventing and treating diseases of protein folding, such as Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis (ALS), cancer, cystic fibrosis and type 2 diabetes.

Related Articles


To do its job properly within the cell, a protein first must fold itself into the proper shape. If it doesn't, trouble can result. More than 300 diseases have at their root proteins that misfold, aggregate and eventually cause cellular dysfunction and death.

The new Northwestern research identifies new genes and pathways that prevent protein misfolding and toxic aggregation, keeping cells healthy, and also identifies small molecules with therapeutic potential that restore health to damaged cells, providing new targets for drug development.

The genetic screening study is published by the journal PLoS Genetics. The small molecule study is published by the journal Nature Chemical Biology.

"These discoveries are exciting because we have identified genes that keep us healthy and small molecules that keep us healthy," said Richard I. Morimoto, who led the research. "Future research should explain how these two important areas interact."

Morimoto is the Bill and Gayle Cook Professor of Biology in the department of molecular biosciences and the Rice Institute for Biomedical Research in Northwestern's Weinberg College of Arts and Sciences. He also is a scientific director of the Chicago Biomedical Consortium.

The genetic study reported in PLoS Genetics was conducted in the transparent roundworm C. elegans, which shares much of the same biology with humans. The small animal is a valued research tool because of this and also because its genome, or complete genetic sequence, is known.

In the work, Morimoto and his team tested all of the approximately 19,000 genes in C. elegans. They reduced expression of each gene one at a time and looked to see if the gene suppressed protein aggregation in the cell. Did the gene increase aggregation or lessen it or have no effect at all?

The researchers found 150 genes that did have an effect. They then conducted a series of tests and zeroed in on nine genes that made all proteins in the cell healthier. (These genes had a positive effect on a number of different proteins associated with different diseases.)

These nine genes define a core homeostastis network that protects the animal's proteome (the entire set of proteins expressed by the organism) from protein damage. "These are the most important genes," Morimoto said. "Figuring out how nine genes -- as opposed to 150 -- work is a manageable task."

In the Nature Chemical Biology study, Morimoto and his colleagues screened nearly one million small molecules in human tissue culture cells to identify those that restore the cell's ability to protect itself from protein damage.

They identified seven classes of compounds (based on chemical structure) that all enhance the cell's ability to make more protective molecular chaperones, which restore proper protein folding. The researchers call these compounds proteostasis regulators. They found that the compounds restored the health of the cell and resulted in reduction of protein aggregation and protection against misfolding. Consequently, health was restored when diseased animals were treated with the small molecules.

Morimoto and his team then conducted detailed molecular analyses of 30 promising small molecules, representing all seven classes. They discovered some compounds were much more effective than others.

"We don't yet know the detailed mechanisms of these small molecules, but we have identified some good drug targets for further development," Morimoto said.

The PLoS Genetics paper is titled "A Genetic Screening Strategy Identifies Novel Regulators of the Proteostasis Network." M. Catarina Silva, a joint-doctoral student at Northwestern in the Morimoto lab and the University of Lisbon is the first author. The National Institutes of Health, the Huntington's Disease Society of America Coalition for the Cure and the Daniel F. and Ada L. Rice Foundation supported the research.

The Nature Chemical Biology paper is titled "Small-Molecule Proteostasis Regulators for Protein Conformational Diseases." Barbara Calamini, a former postdoctoral fellow at Northwestern who is now a research scientist at Duke University, is the first author. The National Institutes of Health and the Daniel F. and Ada L. Rice Foundation supported the research.


Story Source:

The above story is based on materials provided by Northwestern University. The original article was written by Megan Fellman. Note: Materials may be edited for content and length.


Journal References:

  1. Barbara Calamini, Maria Catarina Silva, Franck Madoux, Darren M Hutt, Shilpi Khanna, Monica A Chalfant, S Adrian Saldanha, Peter Hodder, Bradley D Tait, Dan Garza, William E Balch, Richard I Morimoto. Small-molecule proteostasis regulators for protein conformational diseases. Nature Chemical Biology, 2011; DOI: 10.1038/nchembio.763
  2. M. Catarina Silva, Susan Fox, Monica Beam, Happy Thakkar, Margarida D. Amaral, Richard I. Morimoto. A Genetic Screening Strategy Identifies Novel Regulators of the Proteostasis Network. PLoS Genetics, 2011; 7 (12): e1002438 DOI: 10.1371/journal.pgen.1002438

Cite This Page:

Northwestern University. "New hope for diseases of protein folding such as Alzheimer’s, Parkinson’s diseases, ALS, cancer and diabetes." ScienceDaily. ScienceDaily, 8 January 2012. <www.sciencedaily.com/releases/2012/01/120106135946.htm>.
Northwestern University. (2012, January 8). New hope for diseases of protein folding such as Alzheimer’s, Parkinson’s diseases, ALS, cancer and diabetes. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2012/01/120106135946.htm
Northwestern University. "New hope for diseases of protein folding such as Alzheimer’s, Parkinson’s diseases, ALS, cancer and diabetes." ScienceDaily. www.sciencedaily.com/releases/2012/01/120106135946.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com
Madagascar Working to Contain Plague Outbreak

Madagascar Working to Contain Plague Outbreak

AFP (Nov. 24, 2014) Madagascar said Monday it is trying to contain an outbreak of plague -- similar to the Black Death that swept Medieval Europe -- that has killed 40 people and is spreading to the capital Antananarivo. Duration: 00:42 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