A new study suggests that a common hypertension drug may offer a more effective way to treat Parkinson's disease. A malfunctioning protein causing toxic clumps to form in the brains of Parkinson’s disease patients also causes immune cells to trigger inflammation, the study has revealed, which means a drug already approved to treat hypertension may offer a more effective treatment.
"The results help uncover some of the molecular mysteries of neurodegenerative diseases," particularly when it comes to the abnormal accumulation of a protein called α-synuclein, the team from Georgetown University Medical Centre in the US reports in a press release.
While little is known about how the α-synuclein protein is produced, scientists do know that it’s able to change shape - or misfold - rapidly, which makes it toxic. If it's released into the central nervous system, the protein activates a type of immune cell called microglia.
"The real job of microglia is to keep the brain healthy by getting rid of pathogens as well as cellular debris," says lead researcher and neuroscientist, Kathleen Maguire-Zeiss. "However, in a diseased state, microglia can become chronically activated, leading to a continuous onslaught of inflammation, which is damaging to the brain."
Maguire-Zeiss and her colleagues found that α-synuclein had to be of a certain size to influence the release of microglia cells, and when it did, it targetted their 'pattern recognition receptors', which messed with their ability to identify and fight potential pathogens.
Because microglia cells employ a large number of receptors to watch out for pathogens, Maguire-Zeiss and her team needed to figure out which one specifically reacted to the dodgy α-synuclein protein. They found that α-synuclein actually caused two of these 'policing' receptors to come together, set off their 'alarm', and jump-start unneccesary inflammation.
The final stage of their study was to figure out if any drugs available for treating inflammation would have a positive effect. They tried one that was developed by researchers at the University of Colorado in the US to target this combined receptor, and another called Candesartan, which targets just one of the police receptors. Maguire-Zeiss and her team found that this drug significantly reduced inflammation in mouse cells caused by malfunctioning α-synuclein.
Maguire-Zeiss says the success of the drugs shows that they were on the money about which receptors were at work. They now need to figure out how these findings could influence Parkinson's treatment, moving from mouse models to experiments with human cells.
The results have been published in Science Signaling.