Navigation Links
Key stress protein linked to toxicities responsible for Parkinson's, Alzheimer's

Researchers at the Burnham Institute for Medical Research have discovered a mechanistic link between cellular stress caused by free radicals and accumulation of misfolded proteins that lead to nerve cell injury and death in neurodegenerative disorders such as Alzheimer's and Parkinson's Disease.

That link is Protein Disulphide Isomerase (PDI), a chaperone protein that is necessary for proper protein folding in times of cellular stress. Published in today's issue of Nature, these findings revealed that in patients with Alzheimer's and Parkinson's Disease, overproduction of free radicals, specifically nitric oxide (NO), causes inhibition of PDI by a reaction called S-nitrosylation, thereby reducing PDI's neuroprotective benefits. This data provides the first molecular link between NO free radicals and protein misfolding, which is currently thought to be a common pathway in the pathogenesis of virtually all neurodegenerative conditions. Such conditions also include ALS (or Lou Gehrig's disease), Huntington's disease, and many others. Understanding the PDI pathway may lead to the development of new therapeutic approaches for these neurodegenerative diseases and other disorders associated with abnormal protein accumulations due to cellular stress.

"To our knowledge, this is the first published evidence of a link between protein misfolding due to enzymatic machinery malfunction found in a number of degenerative diseases and free radical stress in nerve cells," said Stuart A. Lipton, M.D., Ph.D., Professor and Director of the Del E. Webb Center for Neurosciences and Aging at the Burnham Institute and senior author of the study. Dr. Lipton is also a clinical neurologist in La Jolla. "Our data demonstrate a previously unrecognized relationship between NO and protein misfolding in degenerative disorders, showing that PDI can be a target of NO in cellular models of Parkinson's disease and human neurodegenerative disease."

A protein's structure determines its function. Genetic defects as well as exposure to free radicals or possibly other types of cellular stress can cause small structural defects that lead to protein misfolding. If the misfolded proteins cannot be refolded properly or degraded, they may build up in the cell to cause dysfunction. Defects in either the protein folding or degradation pathways can lead to accumulation of misfolded proteins. The accumulation of misfolded proteins is a common pathogenic mechanism in many diseases, including neurodegenerative disorders.

In normal circumstances, PDI levels increase in response to accumulation of misfolded proteins due to cellular stress. PDI acts as a chaperone for aggregated proteins, rearranging their chemical bonds and thus refolding the proteins to function normally. The new research by Dr. Lipton and his colleagues shows that molecules related to the free radical NO, which is present in elevated levels in neurodegenerative diseases, attacks PDI via a chemical S-nitroyslation reaction, altering PDI's structure and blocking its normal neuroprotective function, which ultimately leads to nerve cell injury and even death. These new results also show that this altered form of PDI is present in elevated amounts in patients with Alzheimer's and Parkinson's Disease, indicating that it is a potential marker for the disease as well as a potential therapeutic target.


'"/>

Source:Burnham Institute


Related biology news :

1. A little stress gives beneficial oomph! to immune system
2. Immune systems distress signal tells bacteria when to strike back
3. Scientists discover the bodys marijuana-like compounds are crucial for stress-induced pain relief
4. Endocannabinoids ?the brains cannabis ?demonstrate novel modes of action to stress
5. Penguin chicks exposed to human visitors experience spike in stress hormone
6. Researchers unravel DNA tangles and enzyme seamstresses
7. Just like us, social stress prompts hamsters to overeat, gain weight
8. Newborn screening can cause unnecessary parental stress
9. Adults who go to bed lonely get stress hormone boost next morning
10. Coral stress like never in history
11. New compound prevents alcoholic behavior, relapse in animals by blocking stress response
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/31/2016)... -- Genomics firm Nabsys has completed a financial  restructuring under ... M.D., who returned to the company in October 2015. ... including Chief Technology Officer, John Oliver , Ph.D., ... Vice President of Software and Informatics, Michael Kaiser ... Bready served as CEO of Nabsys from 2005-2014 and ...
(Date:3/23/2016)... 2016 Einzigartige ... und Stimmerkennung mit Passwörtern     ... MESG ), ein führender Anbieter digitaler Kommunikationsdienste, ... SpeechPro zusammenarbeitet, um erstmals dessen Biometrietechnologie einzusetzen. ... Möglichkeit angeboten, im Rahmen mobiler Apps neben ...
(Date:3/22/2016)... and SANDY, Utah , March ... operates the highest sample volume laboratory in ... and UNIConnect, leaders in clinical sequencing informatics and molecular ... of a project to establish the informatics infrastructure for ... NSO has been contracted by the Ontario Ministry ...
Breaking Biology News(10 mins):
(Date:4/27/2016)... ... April 27, 2016 , ... Cambridge Semantics, ... web technology, today announced that it has been named to The Silicon Review’s “20 ... services and other markets, Cambridge Semantics serves the needs of end users facing some ...
(Date:4/27/2016)... Md. and RESEARCH TRIANGLE PARK, ... Corporation (NASDAQ: UTHR ) announced today that ... Officer, of United Therapeutics will provide an overview and ... 41 st Annual Health Care Conference. ... 2016, at 10:00 a.m. Eastern Time, and can be ...
(Date:4/27/2016)... ... April 27, 2016 , ... Global Stem Cells ... Advisory Board. Ross is the founder of GSCG affiliate Kimera Labs in Miami. , ... he studied hematopoietic stem cell transplantation for hematologic disorders and the suppression of graft ...
(Date:4/26/2016)... ... April 26, 2016 , ... BaseHealth , ... joined the company as Chief Business Officer. Arianpour, a genomics pioneer and visionary ... market, was most recently Chief Commercial Officer of Pathway Genomics. He has held ...
Breaking Biology Technology: