A team of researchers affiliated with multiple institutions in Japan has identified a potential new target for treating Parkinson’s disease. In their paper published in the journal Science, the group describes analyzing various biomarkers associated with Parkinson’s disease and discovering mechanism-based mechanisms of action.
Parkinson’s disease is a neurodegenerative disorder that affects nerve cells of the brain. In Parkinson’s disease patients, certain chemical symptoms occur and gradually damage the nerve cells—hardly imperceptible. Researchers in the United States and Japan have observed a link between Parkinson’s and one of the key biochemical pathways of cellular repair—the enzyme ADAR1. While treatment studies have shown improvement in symptoms in patients with Parkinson’s disease, ADAR1 has remained a focus for research. One such attempt at attempting to treat the disease was by co-author Dr.
Jay Nataro of the University of Tokyo and the Center for Neurodegenerative Disease Research at Nagoya University. Nataro and his team looked for channels regulated by ADAR1 and abnormal ADAR1 expression in cultured cells to see if such channels might be therapeutic targets for Parkinson’s.
To better understand ADAR1, the researchers conducted HPLC profiling of proteins involved in ADAR1 monitoring—about a dozen proteins that were target of antibodies carried out by the team. “We used a very interesting HPLC-based assay involving a combination of chemo-mass spectrometry and RT-PCR detection at targets of ADAR1,” the researchers report.
The researchers report that the ADAR1-targeting compound was found in both healthy and Parkinson’s-affected mice. This observation was fully reproduced in patients with Parkinson’s and AD retrotransposon-lik gene mutations. They also report finding the compound in a fatty acid that altered ADAR1 expression and reduced ADAR1 function—and this confirmed to be the case in patients with AD.
The researchers suggest that ADAR1 inhibition may be beneficial for patients with Parkinson’s—it has been found that inhibition prevents toxic bleeding through Parkinson’s membrane involving an ion channel known as ‘Melanine-transferrin transmembrane protein 1 receptor’ (TTP1R), which is thought to cause AD. Additionally, treatment with an ADAR1 blocking compound reduced progression of TTP1R-dependent blood vascular barriers, indicating that the compound has potential for drug discovery.