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:12/15/2016)... and BADEN-BADEN, Germany , December 15, ... global financial services provider, today announced an agreement with NuData ... biometrics, to join forces. The partnership will enable clients to ... in compliance with local data protection regulation. ... In order to provide ...
(Date:12/15/2016)... ... has announced the addition of the "Global Military Biometrics Market 2016-2020" ... global military biometrics market to grow at a CAGR of 7.5% during ... on an in-depth market analysis with inputs from industry experts. The report ... The report also includes a discussion of the key vendors operating in ...
(Date:12/15/2016)... HILLS, Mich. , Dec. 15, 2016  There ... unlocking car doors or starting the engine. Continental will ... in Las Vegas . Through the ... (Passive Start and Entry) and biometric elements, the international ... field of vehicle personalization and authentication. "The ...
Breaking Biology News(10 mins):
(Date:1/18/2017)... 2017   Parent Project Muscular Dystrophy (PPMD) , ... Duchenne muscular dystrophy (Duchenne) , today announced a $600,000 ... of Technology (NJIT) and Talem Technologies (Talem) as part ... to assist people living with Duchenne. PPMD is ... an embedded computer, software, a force sensor and a ...
(Date:1/18/2017)... ... January 18, 2017 , ... Total Orthopedics and Sports Medicine ... Solofuse-P™. The operation took place on Wednesday, January 11, 2017 at Long Island ... anterior cervical discectomy and fusion on a 42 year old female who was ...
(Date:1/18/2017)... ... January 18, 2017 , ... Announced in December ... Institutes (MII). U.S. Secretary of Commerce Penny Pritzker has announced the award of ... of Defense has announced the award of a new Advanced Regenerative Manufacturing Institute ...
(Date:1/18/2017)... ... 18, 2017 , ... Researchers from a new study are stating that if levels ... prostate cancer treatment, this indicates there is still remaining prostate cancer cells that are more ... PSA test has always been an indicator of whether a man’s prostate cancer is ...
Breaking Biology Technology: