Note: CTSI's Catalyst Awards program supported this research by Pamela England during her participation in the Spring 2014 cycle.
Successful Pharmacological Activation of Nurr1 Opens Doors to Novel Therapies for Incurable Movement Disorder
By Nicholas Weiler via UCSF.edu
UC San Francisco researchers have for the first time developed a strategy for targeting a key molecule implicated in Parkinson’s disease, opening up a potential new treatment strategy for the currently incurable movement disorder.
“This molecule is widely regarded as one of the top therapeutic targets for Parkinson’s disease, but this is the first convincing evidence that it can be directly drugged,” said Pamela England, PhD, an associate professor of pharmaceutical chemistry in UCSF’s School of Pharmacy, and of cellular and molecular pharmacology in UCSF’s School of Medicine, who was the senior author of the new study, published March 7, 2019, in Cell Chemical Biology.
Parkinson’s disease affects 10 million people worldwide with progressively worsening movement difficulties as well as cognitive and mood-related symptoms, all of which are caused by degeneration of midbrain neurons that produce the neurotransmitter dopamine. For the vast majority of Parkinson’s patients, their disease has no obvious genetic or environmental cause, and there is currently no treatment to prevent or slow the disease. Existing drugs only temporarily boost dopamine signaling to soften the disease’s symptoms, and can lead to serious side effects.
Over the past decade, promising research has shown that before dopamine neurons begin to degenerate, they first stop making dopamine, suggesting that defects in the molecular pathway that produces and stores dopamine may be a culprit in the cells’ eventual demise. A prime suspect in this chain of events is the transcription factor Nurr1, a gene-activating protein that is critical for the survival of dopamine neurons, and also regulates many aspects of their dopamine production and storage. Research in genetically modified mice has found that too little Nurr1 can lead to Parkinson-like symptoms, which can be cured by genetically elevating Nurr1 levels.