Adjust Text Size:change font sizechange font sizechange font sizechange font sizechange font sizechange font size

Light of Day Foundation Challenge

Light of Day Challenge

Goal: $100,000

Raised: $66,827

 

Donate Now

 

Educational Materials

  publications

Do you want to know more about Parkinson's? PDF's materials provide information about symptoms, medications, resources & more.

Order Free Materials Today

Parkinson's HelpLine

 


Science News

Structure of Alpha-Synuclein Protein Takes Surprising Twist

Researchers recently discovered that alpha-synuclein (α-synuclein) — a protein that forms clumps called Lewy bodies in the brain cells of people with Parkinson’s disease (PD)— exists in cells in a radically different form than they previously thought. This finding provides new clues about the causes of Parkinson’s, as well as suggests new strategies for treatment. The study was published in the August 14, 2011 issue of Nature.

By studying the human brain, scientists have been able to link Lewy bodies with the brain cell death that triggers PD. Although scientists do not know exactly what causes α-synuclein to form toxic protein clumps, the answer almost certainly has to do with changes in the protein’s structure.

Most proteins, which are composed of long chains of amino acids, fold upon themselves into complex three-dimensional structures that give them their unique properties. Until now, researchers thought that α-synuclein was one of the minority of proteins in cells that existed as a floppy, unfolded chain. This might have helped to explain the protein’s tendency to form clumps.

But researchers led by Dennis Selkoe, M.D., at Harvard Medical School questioned this school of thought, wondering if α-synuclein only appeared to be unstructured because of the methods scientists were using to study it. Most previous studies used α-synuclein produced in bacteria or analyzed under harsh conditions that could disrupt the natural protein structure. So Dr. Selkoe and his colleagues studied α-synuclein purified from human cells using several gentler methods.

Results

  • Instead of being unfolded, α-synuclein in human cells adopts a twisted structure known as an α-helix.
  • Four of these α-helical protein molecules join together to form a tetramer in cells.
  • The α-synuclein tetramer did not clump together like the single, unfolded α-synuclein molecule that scientists had studied previously.

What Does it Mean?

A protein’s structure provides valuable clues to its function. Scientists still do not know exactly what role α-synuclein plays in healthy cells. However, α-synuclein deposits are the hallmark of the pathological changes in brains of people with PD. Many scientists believe that if we find a way to prevent its accumulation, we may be able to stop and potentially reverse the damage these deposits may cause to the brain. Therefore, a better understanding of α-synuclein’s structure and function might help scientists figure out what causes the protein to form Lewy bodies in PD.

Importantly, the α-synuclein tetramer resisted clumping together. This result suggests that in PD, the tetramer may fall apart into individual α-synuclein molecules that can then cluster into Lewy bodies. By designing new drugs that stabilize the α-synuclein tetramer, scientists might someday be able to reduce the formation of Lewy bodies in people with PD.

Reference: Bartels, T., Choi, J. G., & Selkoe, D. J. (2011). α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation Nature, 477(7362), 107–110. doi:10.1038/nature10324  PubMed PMID: 21841800; PubMedCentral PMCID: PMC3166366.

Source Date: Sep 19 2011