Archive for the ‘Natural biology’ Category
A key protein that may prevent the development of neurodegenerative
The protein alpha-syncline seems to have a radically different structure in healthy cells to that seen in previous research, challenging existing paradigms about Parkinson, suggesting a new therapeutic approach. “The data show that alpha-syncline is wrongly characterized as a natively unstructured protein,” explains one of the principal authors of the research, Dennis Sloe. “This discovery is of fundamental importance for understanding both how normal alpha-syncline to know how this protein is impaired in Parkinson’s” details.
When it comes to proteins, function follows form. A protein is a chain of amino acids, usually bent in an exquisite three-dimensional structure. Each twist and turn in the chain contributes to the unique properties of this protein and its behavior, important issues for scientists to accurately describe the arrangement of the folds but sometimes you get a wrong model.
The new study suggests that this is precisely what happens with alpha-syncline, a protein that forms the so-called Lowy bodies in the brains of patients with Parkinson’s and related disorders. Scientists have long assumed that alpha-syncline occurs in healthy cells as a monomer, a chain coiled like a serpent writhing. However, Sloe’s team has shown that the structure is much more organized and sophisticated.
“This will open up some new therapeutic doors. Everyone thought that the protein unfolded, so that pharmaceutical companies have focused on preventing the development of alpha-syncline from the aggregation, “says another of the principal authors of the study, Tim Bartels. They knew that alpha-syncline was abundant in the brain before taking the connection between this protein and Parkinson’s in 1997. Experiments in the 90′s indicated that the protein is stable when exposed to conditions that tend to alter the structure of most proteins.
Sloe Bartels and wondered whether the laboratories were ignoring important aspects of the natural biology of this protein, so they designed experiments to analyze the behavior of alpha-syncline, using gentler methods. The trend continued to work with protein obtained from human cells rather than from engineered bacteria. The aim was to gain new insights into the behavior of the group of alpha-syncline.
Thus, the researchers found that alpha-syncline was tetramer and was the dominant form of the protein in healthy human cells and also showed a remarkable resistance to aggregation. The tetramers retained their original structure for 10 days throughout the experiment. In stark contrast, the alpha-syncline monomers form groups began after a few days and ended up as large aggregates called amyloidal fibrils. According to experts, the Lowy bodies that accumulate in the brains of Parkinson’s patients are mainly amyloidal fibers.