Researchers find new clues about protein linked to Parkinson's disease

Jun 17, 2011

Researchers at the Keck School of Medicine of the University of Southern California (USC) have uncovered structural clues about the protein linked to Parkinson's disease (PD), which ultimately could lead to finding a cure for the degenerative neurological disorder.

The alpha-synuclein (α-synuclein) protein is commonly found in the healthy human brain even though its function is not clear. The protein has been the subject of substantial Parkinson's research, however, because it is a major component in the protein clumps found in PD cases.

Unlike most proteins, which are typically rigid and occur in one definitive form, the alpha-synuclein protein can fold and change its structure. Researchers Tobias S. Ulmer, Ph.D. and Sowmya Bekshe Lokappa, Ph.D. at the Keck School-affiliated Zilkha Neurogenetic Institute have determined that the energy difference between two particular alpha-synuclein structures is less than previously speculated.

Their study, to be published in the June 17 issue of The Journal of Biological Chemistry, is the first to quantify that energy difference, 1.2±0.4 kcal/mol.

"We're trying to understand the mechanisms of protein folding and misfolding," said Ulmer, the study's principal investigator and an assistant professor in the Department of Biochemistry and Molecular Biology at the Zilkha Neurogenetic Institute. "Then we can say why something is going wrong, which is essential to treating neurodegenerative disorders like Parkinson's."

If proteins misfold, they are repaired or they break down. However, when alpha-synuclein misfolds it aggregates and becomes toxic to surrounding nerve cells, Ulmer said. Understanding its folding and finding what causes aberrant folding is therefore key to determining the root cause of the disorder, he added.

To put the discovery into perspective, Ulmer compared the energy that researchers thought was needed to change the protein's structure to hurricane-force winds and the actual energy required to a light summer breeze. The experiments were conducted in 2010, measuring the energy of elongated and broken helix forms of alpha-synuclein through circular dichroism spectroscopy, fluorescence spectroscopy and isothermal titration calorimetry.

"There may be a continuous interconversion between folded alpha-synuclein structural states that might contribute to its pathological misfolding," said Lokappa, a post-doctoral research associate at the Center for Craniofacial Molecular Biology at USC and the study's co-author. "But we need to have even better insight into the mechanisms of folding and misfolding to explain what's going wrong in the brain."

The paper is the sixth in a series of studies that Ulmer has published on .

Parkinson's is a neurological disorder that has no cure or determined cause. It is a slow-progressing degenerative disease that most commonly affects motor function. According to the National Parkinson Foundation, the disorder is the second-most common neurodegenerative disease after Alzheimer's, affecting 1 million people in the United States and some 4 million worldwide.

Explore further: Major step forward in understanding of viruses as scientists unlock exact structure of Hep A virus

More information: www.jbc.org/content/286/24/21450.full

Related Stories

Yeast holds clues to Parkinson's disease

Sep 09, 2010

Yeast could be a powerful ally in the discovery of new therapeutic drugs to treat Parkinson's disease says a scientist presenting his work at the Society for General Microbiology's autumn meeting in Nottingham today.

Toxicity mechanism identified for Parkinson's disease

Jan 02, 2009

Neurologists have observed for decades that Lewy bodies, clumps of aggregated proteins inside cells, appear in the brains of patients with Parkinson's disease and other neurodegenerative diseases.

Unfolding pathogenesis in Parkinson's

Jan 19, 2011

The study, published in the Journal of Clinical Investigation, reveals that damaged alpha-synuclein proteins (which are implicated in Parkinson's disease) can spread in a 'prion-like' manner, an infection model previously descri ...

Key Parkinson's clue could be protein aggregate

Nov 03, 2010

(PhysOrg.com) -- Proteins perform almost every function our bodies require for life. But, they also can misbehave in myriad ways. By retracing the history of each abnormal reaction, biochemists aim to determine ...

Recommended for you

World's fastest manufacture of battery electrodes

24 minutes ago

New world record: Scientists at the Karlsruhe Institute of Technology (KIT) increased the manufacturing speed of electrode foils coated batch-wise by a factor of three – to 100 meters per minute. This was ...

Waste, an alternative source of energy to petroleum

25 minutes ago

The group led by Martín Olazar, researcher in the UPV/EHU-University of the Basque Country's Department of Chemical Engineering, is studying the development of sustainable refineries where it is possible ...

Researchers developing new thermal interface materials

1 hour ago

In the microelectronics world, the military and private sectors alike need solutions to technologic challenges. Dr. Mustafa Akbulut, assistant professor of chemical engineering, and two students lead a project ...

New insights on carbonic acid in water

15 hours ago

Though it garners few public headlines, carbonic acid, the hydrated form of carbon dioxide, is critical to both the health of the atmosphere and the human body. However, because it exists for only a fraction ...

User comments : 0