Featured Research

from universities, journals, and other organizations

Not guility: Parkinson and protein phosphorylation

Date:
August 26, 2013
Source:
Ecole Polytechnique Fédérale de Lausanne
Summary:
Clues left at the scene of the crime don't always point to the guilty party, as researchers investigating Parkinson's disease have discovered. It is generally accepted that the disease is aggravated when a specific protein is phosohorylated -- that is to say chemically transformed -- by an enzyme. Now neuroscientists have been able to show that, on the contrary, this transformation tends to protect against the progression of the disease. This conclusion could change therapeutic approaches currently being developed by pharmas.

Clues left at the scene of the crime don't always point to the guilty party, as EPFL researchers investigating Parkinson's disease have discovered. It is generally accepted that the disease is aggravated when a specific protein is transformed by an enzyme. The EPFL neuroscientists were able to show that, on the contrary, this transformation tends to protect against the progression of the disease. This surprising conclusion could radically change therapeutic approaches that are currently being developed by pharmaceutical companies.

The research is to appear in an article in the Proceedings of the National Academy of Sciences (PNAS).

Parkinson's disease is characterized by the accumulation of a protein known as alpha-synuclein in the brain. If too much of it is produced or if it's not eliminated properly, it then aggregates into small clumps inside the neurons, eventually killing them. Several years ago scientists discovered that these aggregated proteins in the brain had undergone a transformation known as "phosphorylation" -- a process in which an enzyme adds an extra chemical element to a protein, thus modifying its properties.

The investigators' conclusion that the enzyme's activity could be responsible for the disease seems eminently reasonable. If phosphorylation and protein aggregation go hand in hand, then it makes sense that one should cause the other. This is the assumption that researchers and pharmaceutical companies made as they tried to reduce the phosphorylation by deactivating an enzyme involved in the process. But they have been following a false lead, as the EPFL team was able to show.

The scientists even discovered that the phosphorylation of the protein has positive effects. On the one hand, it considerably reduces the toxic aggregation of the protein, and on the other, it helps the cell eliminate the protein. "The two phenomena are undoubtedly related, and together could play a role in the reduction of alpha-synuclein toxicity, but we don't yet understand the impact of both processes at each stage of the disease," explains neurobiologist Abid Oueslati, first author on the study.

Going back to the beginning

To reach this conclusion, the biologists had to explore the initial disease conditions. They injected into rat neurons what were thought to be the elements needed to trigger the disease: an overexpression of alpha-synuclein and the enzyme that phosphorylates it (PLK2).

To their surprise, the group of animals subjected to both of the parameters -- overproduction of the protein and phosphorylation -- lost nearly 70% fewer neurons than another group in which only the protein was overexpressed. Consequently, they had fewer lesions, and less Parkinson symptoms.

"We owe this discovery to unique tools that we developed, in collaboration with the Aebischer group, in order to study the effect of this transformation at the molecular level. ," explains Hilal Lashuel, who directed the study. Our study revealed the limitations of the most commonly used approach, which uses genetic mutations to mimic this process.

Lashuel thinks it is highly probable that the phosphorylation of the proteins takes place after they are aggregated, that is to say once the disease is already established. Or it could be a defense mechanism of the neurons, an attempt to try and slow down the progression of the disease from the beginning.

The scientists' research opens doors for the development of future drug therapies. "The lesson we learned from this research is that everything you find at the scene of a crime is not necessarily involved in the crime. By remaining fixated on that assumption, we may lose sight of the bigger picture."


Story Source:

The above story is based on materials provided by Ecole Polytechnique Fédérale de Lausanne. Note: Materials may be edited for content and length.


Cite This Page:

Ecole Polytechnique Fédérale de Lausanne. "Not guility: Parkinson and protein phosphorylation." ScienceDaily. ScienceDaily, 26 August 2013. <www.sciencedaily.com/releases/2013/08/130826182919.htm>.
Ecole Polytechnique Fédérale de Lausanne. (2013, August 26). Not guility: Parkinson and protein phosphorylation. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2013/08/130826182919.htm
Ecole Polytechnique Fédérale de Lausanne. "Not guility: Parkinson and protein phosphorylation." ScienceDaily. www.sciencedaily.com/releases/2013/08/130826182919.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

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
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) — Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) — At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) — The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
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