A balancing act in Parkinson's disease: Phosphorylation of alpha-synuclein

October 12, 2009

Both genetic and pathologic data indicate a role for the neuronal protein alpha-synuclein in Parkinson disease. Previous studies have indicated that phosphorylation of alpha-synuclein at amino acid 129 (Ser129) is a key event in alpha-synuclein-mediated nerve cell toxicity. However, Mel Feany and colleagues, at Brigham and Women's Hospital, Boston, have now identified a counterbalancing role in nerve cell protection for phosphorylation of alpha-synuclein amino acid 125 (Tyr125).

In the study, of human alpha-synuclein Tyr125 was detected in transgenic for human alpha-synuclein and shown to protect from alpha-synuclein-mediated nerve cell toxicity in a Drosophila model of Parkinson disease. That the two phosphorylated amino acids have opposing roles was indicated by the observation that Tyr125 phosphorylation decreased levels of toxic soluble alpha-synuclein oligomers in the Drosophila , whereas Ser129 phosphorylation increased them.

More importantly, Tyr125 phosphorylation was found to decrease as both humans and Drosophila aged and was reduced in cortical tissue from patients with synucleinopathy with Lewy bodies, a disease related to Parkinson disease. The authors therefore suggest that changes in the balance between Ser129 and Tyr125 phosphorylation — which promote nerve cell toxicity and protection, respectively — might cause alpha-synuclein-mediated nerve cell toxicity in Parkinson disease and related disorders.

More information: View this article at: www.jci.org/articles/view/3908 … 59af0a7e79b38662c2ee

Source: Journal of Clinical Investigation

Related Stories

Recommended for you

Fabric imbued with optical fibers helps fight skin diseases

February 23, 2018
A team of researchers with Texinov Medical Textiles in France has announced that their PHOS-ISTOS system, called the Fluxmedicare, is on track to be made commercially available later this year. The system consists of a piece ...

DNA gets away: Scientists catch the rogue molecule that can trigger autoimmunity

February 22, 2018
A research team has discovered the process - and filmed the actual moment - that can change the body's response to a dying cell. Importantly, what they call the 'Great Escape' moment may one day prove to be the crucial trigger ...

Low-calorie diet enhances intestinal regeneration after injury

February 22, 2018
Dramatic calorie restriction, diets reduced by 40 percent of a normal calorie total, have long been known to extend health span, the duration of disease-free aging, in animal studies, and even to extend life span in most ...

Artificial intelligence quickly and accurately diagnoses eye diseases and pneumonia

February 22, 2018
Using artificial intelligence and machine learning techniques, researchers at Shiley Eye Institute at UC San Diego Health and University of California San Diego School of Medicine, with colleagues in China, Germany and Texas, ...

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

Breakthrough could lead to better drugs to tackle diabetes and obesity

February 22, 2018
Breakthrough research at Monash University has shown how different areas of major diabetes and obesity drug targets can be 'activated', guiding future drug development and better treatment of diseases.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.