Getting Back to Basics with Parkinson's Disease

"At UCSF, we are encouraged to think outside the box and to pursue different ideas." Robert Edwards, MD

Dr. Robert Edwards has always believed in the importance of getting back to basics. If you want to understand how the brain works, he says, you have to understand synapses, the central structures of the brain. But to get there, you first need a strong grasp of how synapses work, beginning with the release of neurotransmitters. That’s why, for 25 years, the UCSF professor of neurology and physiology has been hyper-focused on understanding this phenomenon. Using his background in this area, he has homed in on alpha-synuclein, a specific protein involved in this process. Now, with the support of the Weill Innovation Award, Dr. Edwards aims to delve deeper into the protein, exploring its dual – though perhaps not contradictory – roles in both Parkinson’s disease and normal brain health.

On the origin of this work: “Twenty years ago, Robert Nussbaum, MD – who is now at UCSF – found a mutation in alpha-synuclein that caused Parkinson’s disease. It led to a rebirth of curiosity-driven research in Parkinson’s because it was the first causative gene identified. Interestingly, only a small number of people with Parkinson’s have this mutation or any of the other mutations that have since been identified in synuclein. But even without the mutation, men and women with Parkinson’s still experience a massive accumulation of the protein in their brains. It therefore plays a central role in the most common form of the disease, but we still don’t know what that role is.”

It’s the volume that matters: “I think alpha-synuclein levels normally rise and fall, serving some adaptive value. But if they go up for too long – likely in response to something that’s dangerous for the brain – then the patient may develop Parkinson’s disease. That’s why I really want to understand the function of the protein. It will tell me why alpha-synuclein levels rise and fall. If we know why they vary, we’ll have taken the first step in understanding what causes Parkinson’s, and we’ll know why the protein is there.”

Why a traditional drug might not be the answer: “I would not want to inhibit the normal function of synuclein; I think that would have negative effects. But by understanding why its levels fluctuate, I hope to find a way to prevent it from going up in the first place, thus preventing Parkinson’s disease. It might be that you need to protect your brain from certain factors. A drug might not be the way to do this; it could be something much more holistic.”

Why UCSF is the right place to do this work: “There are many outstanding people here. Individuals with strong opinions – who want to do science that is independent and might buck the prevailing trends – can do well here. We are allowed, even encouraged, to think outside of the box and to pursue different ideas. What I do is not typical in neurodegenerative disease. The same can be said for what Nobel laureate Stan Prusiner, MD, has done for many years.”

Why he’s grateful for the award: It heartens me that Joan and Sandy Weill are supporting scientists who are already here and already pioneering new areas. In addition to expanding our neuroscience community, they’re enabling us to do more with the intellectual resources already at our disposal. New buildings are excellent, but investing in the people that are in the buildings is the most crucial piece of the puzzle. I’m very thankful that they’ve invested in us.”

UCSF Weill Awards

Joseph DeRisi, PhD; Samuel Pleasure, MD, PhD; and Michael Wilson, MD