Are scientists looking for a cure for Parkinson’s disease? – ScienceDaily
A promising molecule in the prevention of Parkinson’s disease has been refined by scientists at the University of Bath in the UK and has the potential to be developed into a drug to treat the fatal neurodegenerative disease.
Professor Jody Mason, who led research at Bath’s Department of Biology and Biochemistry, said: “There is still a lot of work to be done, but this molecule has the potential to be a precursor to a drug. Today there are only drugs to treat the symptoms of Parkinson’s disease – we hope to develop a drug that can make people healthy before symptoms even develop. “
Parkinson’s disease is characterized by a “misfolding” of a specific protein in human cells, where it aggregates and malfunctions. The protein – alpha-synuclein (αS) – is abundant in all human brains. After bad folding, it accumulates in large masses, called Lewy bodies. These masses are made up of S aggregates that are toxic to dopamine-producing brain cells, causing them to die. It is this drop in dopamine signaling that triggers the symptoms of Parkinson’s disease, as the signals transmitted from the brain to the body become loud, resulting in the distinctive tremors seen in people with the condition.
Previous efforts to target and “detoxify” S-induced neurodegeneration have allowed scientists to analyze a large library of peptides (short chains of amino acids – the building blocks of proteins) to find the best candidate for preventing the bad. folding of the αS. Of the 209,952 peptides examined in previous work by scientists in Bath, peptide 4554W has shown the most promise, preventing αS from aggregating into toxic disease forms in laboratory experiments in solutions and on living cells.
In their latest work, this same group of scientists modified the 4554W peptide to optimize its function. The new version of the molecule – 4654W (N6A) – contains two modifications of the parental amino acid sequence and has been shown to be significantly more effective in reducing αS misfolding, aggregation and toxicity. However, even if the modified molecule continues to prove successful in laboratory experiments, it will still take many years to find a cure for the disease.
Dr Richard Meade, lead author of the study, said: “Previous attempts to inhibit alpha synuclein aggregation with small molecule drugs have been unsuccessful because they are too small to inhibit protein interactions. This is why peptides are a good option – because they are large enough to prevent the protein from aggregating, but small enough to be used as a target drug on the alpha synuclein protein to suppress its toxicity. Not only will this research lead to the development of new treatments to prevent the disease, but it will also uncover the fundamental mechanisms of the disease itself, which will allow us to better understand why the protein folds poorly in the first place. “
Prof. Mason added, “Then we’ll work on how we can bring this peptide into the clinic. We need to find ways to further modify it so that it looks more like a drug and can cross biological membranes and enter brain cells. This can mean moving away from natural amino acids towards molecules made in the laboratory. “
This research also has implications for Alzheimer’s disease, type 2 diabetes, and other serious human diseases where symptoms are triggered by improper folding of proteins.
Dr Rosa Sancho, head of research at Alzheimer’s Research UK, said: “Finding ways to prevent alpha synuclein from becoming toxic and damaging brain cells could point to a new path for future drugs for stop devastating diseases like Parkinson’s disease and Lewy body dementia.
“We are delighted to have supported this important work to develop a molecule capable of preventing alpha synuclein from folding. The molecule has been tested in cells in the lab and will need to be developed and tested further before it can be turned into a treatment. This process will take several years, but it is a promising discovery that could pave the way for a new drug in the future.
“Currently, there is no disease-modifying treatment available for Parkinson’s disease or Lewy body dementia, which is why continued investment in research is so important to all who live with these conditions. “
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