Advances in Parkinson’s disease have been linked to the impact on the production of dopamine in the brain, so much research has focused on technologies that can increase the supply of this key neurotransmitter. Scientists at Harvard University and Nanyang Technological University in Singapore have discovered two molecules that show great potential in this regard, promoting the production of dopamine in mice with Parkinson’s disease and thus greatly improving their motor function.
The team’s research focused on a class of proteins called Nurr1, which play a key role in the production of dopamine and in maintaining healthy levels of dopamine in the brain. The team has been looking for molecules that could stimulate Nurr1’s role in Parkinson’s disease, and has found a pair of “molecular pairs” of prostaglandins, which seem promising.
Prostaglandins play a variety of roles in the body, helping to smooth the contraction and relaxation of muscles and blood vessels, as well as helping to regulate inflammation. What do they do dopamine function through Nurr1 dopamine dopallamine do not work for, relatively unknown. But through MRI and X-ray crystallography, the team found two types — precursor adenodein E1 (PGE1) and parathyroid A1 (PGA1), which bind to proteins to increase their activity.
“Given the basic function of Nurr1, we’ve been looking for the activation molecules in the body,” said study leader Professor Yoon Ho Sup of Nanyang Technological University. “Ultimately, we successfully determined that PGE1/PGA1 is a molecular pair that acts specifically on Nurr1, which can lead to neuroprotective effects on the brain. “
The team demonstrated its potential neuroprotective effects by experimenting on cells and then on a live mouse model of Parkinson’s disease. Treated mice with PGE1/PGA1, these molecules were seen binding to Nurr1 and activating Nurr1, which in turn led to a significant increase in dopamine secretion. The mice subsequently showed significant improvement in motor function, a key indicator of the severity of Parkinson’s disease.
Although the study is still in its early stages and more work needs to be done before this approach can be translated into humans, the team is still excited about the results. Other techniques have shown a commitment to improving dopamine production and improved motor function, and researchers believe their new approach is a potential way to slow or stop the disease rather than simply addressing its symptoms. Other experimental treatments, such as deep brain stimulation, also pose a risk of side effects, the team said. But because of the inherent biocompatibility of prostaglandins, this new potential treatment may provide a safer way forward.
“Given that all candidate Stodmo drugs have failed to demonstrate neuroprotection in clinical trials, our findings may provide an opportunity to design a mechanism-based disease modification therapy to treat Parkinson’s disease with small side effects,” Yoon Ho Sup said. “
The findings were published in the journal Nature Chemical Biology.