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.

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 September 23, 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 September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
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