Data from the National Institutes of Health (NIH) indicate that approximately 50,000 people receive a diagnosis of Parkinson’s disease each year in the United States.
In terms of its worldwide prevalence, studies have shown that Parkinson’s disease affects one percent of the population aged 60 and over, and it is the second most widely diagnosed neurodegenerative condition.
Though the causes of this condition remain unclear, its development is associated with certain toxic mechanisms that become established in the brain. One of the main mechanisms is the formation of aggregates known as “Lewy bodies,” which disrupt the normal activity of nerve cells.
These aggregates are made out of a protein called “alpha-synuclein.” Although researchers know that alpha-synuclein plays an important role in Parkinson’s, as well as in different forms of dementia, it remains unclear how it is produced in the body and what role it plays in the healthy brain.
What we do understand, however, is that acting on alpha-synuclein could put a stop to the deterioration of motor function that takes place in Parkinson’s.
Recently, a team of researchers from the Universitat Autònoma de Barcelona in Spain has identified a special molecule that not only blocks neurodegeneration, but can also reverse it.
The study paper, which appears in PNAS, outlines the methods that the researchers used in order to find this molecule — named SynuClean-D — and begin testing it for effectiveness and safety.
The discovery of SynuClean-D
The researchers scanned over 14,000 molecules, looking for a specific feature: molecules that would be able to stop alpha-synuclein from sticking together into aggregates.
By employing novel methods of screening molecules and analyzing their properties, the scientists eventually identified SynuClean-D, which acts as an aggregation inhibitor.
In a further step, they also tested out the molecule in vitro, to see if it would be effective and safe to use in human neural cell cultures. Once this step was cleared, the team decided to also test SynuClean-D in vivo — in the Caenorhabditis elegans worm, which is often used in Parkinson’s research.
C. elegans is a good model for Parkinson’s because it expresses alpha-synuclein in the muscle or in certain nerve cells — namely dopaminergic neurons, which synthesize the key neurotransmitter dopamine.
These types of neurons are also involved in sending the messages that regulate mobility, so when their activity is inhibited by alpha-synuclein aggregates, an individual’s ability to move is also impaired.
The scientists used two C. elegans models of Parkinson’s disease in the current study. After administering SynuClean-D to the worms in food, the researchers found that it hindered alpha-synuclein from sticking together, protected the animals against neural degeneration, and boosted their mobility.
In the future, the researchers hope that their current findings will enable the development of more targeted treatments for neurodegenerative conditions.
“Everything seems to indicate that the molecule we identified, the SynuClean-D, may provide therapeutic applications for the treatment of neurodegenerative diseases such as Parkinson’s in the future.”
Study coordinator, Salvador Ventura
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