Parkinson's disease (idiopathic parkinsonism syndrome) can be defeated.
Parkinson's disease is also known as idiopathic parkinsonism or tremor palsy. It is a slowly progressive chronic neurodegenerative neurological disease. It is the second most common, affecting more than 10 million people worldwide, disease. For better understanding the disease origin, the team of researchers from the United States and Israel have developed an integrative approach. It combines experimental and computational methods. The research was shown how individual proteins can form harmful groups that contribute to the development of the disease. Scientists said their discovery could help to develop new therapies. Thus, it will be possible to delay or even stop the progression of neurodegenerative diseases.
What is alpha synuclein.
Alpha synuclein is a protein that helps to regulate the release of neurotransmitters in the brain and neurons. It exists as a single unit, but usually combines with other units to perform cellular functions. When too many units combine, it can lead to the formation of Lewy bodies. These bodies are associated with neurodegenerative diseases such as Parkinson’s disease and dementia.
Searching for new treatments and medical results.
Researchers of the Pennsylvania State College of Medicine and the Hebrew University of Jerusalem have teamed up to study the different protein conformations called alpha-synuclein. This protein, combined with the formation of harmful aggregates, can lead to the development of neurodegenerative diseases.
Researchers know that aggregates of this protein are the cause of this disease, but still it is not so clear how they are formed. Alpha-synuclein is highly disordered, which means that it exists as an ensemble of different conformations or shapes, rather than as a well-built three-dimensional structure. This characteristic makes difficulties in studying the protein with using standard laboratory methods. But the team of researchers used computers with new experiments´ methods to predict and study the various conformations protein might fold into.
Scientists share their work experience.
“Computational biology allows us to study the forces inside and outside of a protein and what reaction it has” said Nikolai Dokholian, the professor of pharmacology of the College of Medicine and research at the Pennsylvania State Cancer Institute. “We used laboratory experiments by Professor Eitan Lerner at the Department of Biological Chemistry at the Hebrew University of Jerusalem. A number of algorithms show how the specific forces have indluence in and on a particular protein. This allows you to define the different conformations that the protein will take based on these forces. This way we can study the conformations of alpha-synuclein in a way that would be difficult to identify. This is possible only in experimental research. “
In an article published in the journal Structure, May 19, 2021., the researchers writing their detailed methodology of studying the various alpha-synuclein conformations. They used data from previous experiments to program in their calculations the molecular dynamics of the protein. Their experiments revealed the conformational assembly of alpha-synuclein. It is a series of different forms that a protein can take.
“Previous knowledge has shown that this spaghetti-like protein has structural changes in microseconds,” Lerner said. “Our results show that alpha synuclein is stable in certain conformations within milliseconds. This is slower than was supposed to be.”
“We believe we have identified stable forms of alpha synuclein. These forms allow it to form complexes with itself and other biomolecules, ”said Jiaxing Chen, a graduate student of the College of Medicine. “This opens the door to the development of medications that can regulate the protein function.”
Idiopathic Parkinson's Syndrome: Treatment Prospects.
Chen Sofia Zaer’s co-author together with colleagues of the Hebrew University used some of experimental methods. Their goal is to make sure that alpha-synuclein can fold into stable shapes predicted by simulation. The research team continues to study these stable conformations and the entire process of alpha-synuclein aggregation of Parkinson’s disease.
” Our information can be useful to develop small molecules that regulate alpha-synuclein activity,” Lerner said. “Medicines that prevent protein aggregation and improve its normal neurophysiological function may interfere with the development and progression of neurodegenerative diseases.”
