Parkinson’s disease is, today, incurable. It affects between 2% and 5% of those over 65 years of age, hence knowing how the neurodegenerative process that characterizes the disease works has become a crucial issue for scientists.
A team of researchers from the Institute of Biotechnology and Biomedicine of the Autonomous University of Barcelona (Spain) has identified a small molecule known as SynuClean-D as a possible tool to slow down the neurodegenerative processes caused by diseases such as Parkinson’s. E l study was conducted in animal models, particularly in worms and rodents now be tested.
The SynuClean-D molecule manages to interrupt the formation of amyloid alpha-synuclein fibers responsible for the onset of Parkinson’s disease, and reverses the neurodegeneration caused by this disease, which represents the second most common incurable neurodegenerative disorder after Alzheimer’s.
Parkinson’s disease is characterized by the accumulation of protein deposits in dopaminergic neurons in the form of amyloid fibers. These clumps are entangled by the alpha-synuclein protein, which makes it difficult to identify molecules that could prevent or reverse the process and the associated neurodegeneration.
Now, this team of Spanish scientists, after analyzing more than 14,000 molecules, discovered that the SynuClean-D molecule inhibited the aggregation of the alpha-synuclein protein and broke the already formed amyloid fibers, thus preventing the start of the process that causes the appearance of the illness.
As stated in their study published in the journal PNAS, in experiments carried out with the small worm Caenorhabditis elegans , one of the most widely used animal models in neurodegenerative diseases, scientists were able to verify that when administered through food, the molecule was capable of markedly reduce alpha-synuclein incorporations, thus preventing the spread of toxic aggregates and, therefore, preventing the degeneration of dopaminergic neurons.
“Everything seems to indicate that the molecule we identified, SynuClean-D, may provide therapeutic applications for the treatment of neurodegenerative diseases such as Parkinson’s in the future”, comments Salvador Ventura, leader of the work.
To achieve this milestone, the experts developed a methodology capable of identifying alpha-synuclein attachment inhibitors among thousands of molecules. Once recognized, they carried out an in vitro biophysical characterization of its inhibitory activity and performed tests to discover its behavior with cultures of human neural cells, before testing it in worms. These small animals ( Caenorhabditis elegans) express alpha-synuclein in muscle or dopaminergic neurons.
The experiments showed that the administration of the SynyClean-D inhibitor reduced the sum of proteins, improving the mobility of the animal and protecting it from neural degeneration.
The researchers hope that this finding will contribute in the future to developing a therapeutic tool to treat this disease.
Reference: Jordi Pujols, Samuel Peña-Díaz, Diana F. Lázaro, Francesca Peccati, Francisca Pinheiro, Danilo González, Anita Carija, Susanna Navarro, María Conde-Giménez, Jesús García, Salvador Guardiola, Ernest Giralt, Xavier Salvatella, Javier Sancho, Mariona Sodupe, Tiago Fleming Outeiro, Esther Dalfó, Salvador Ventura. Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons . Proceedings of the National Academy of Sciences , 2018; 201804198 DOI: 10.1073 / pnas.1804198115
