MBI researchers shed light on process of neurodegeneration

Over the last few years, there has been great interest in learning more about the proteins that accumulate in brains affected by various neurodegenerative disorders and the idea that these proteins can spread from one area of the brain to the other.

Now, a team of University of Florida neuroscientists has published findings that shed new light on the mechanisms helping to explain the process of neurodegeneration in diseases such as Parkinson’s disease.

In a paper published in the journal Molecular Neurodegeneration and cited by the news website Alzforum in June, a team led by Paramita Chakrabarty, Ph.D., assistant professor of neuroscience, and Benoit Giasson, Ph.D., professor of neuroscience, revealed findings that are important in understanding the pathophysiology of diseases including Parkinson’s disease and the related disorder known as dementia with Lewy bodies.

In particular, the researchers used a mouse model to examine the spread of alpha-synuclein (protein) clumps, which are involved in a number of neurodegenerative diseases, and explored how glial cells — which provide support and protection for neurons — may be responsible for the spread and propagation of this neurodegeneration or the disease itself.

“Previous studies have shown that the majority of this pathology actually jumps from one neuron to another neuron across synapses,” said Chakrabarty, a member of the Evelyn F. and William L. McKnight Brain Institute of the University of Florida. “We said, ‘OK, let’s look at this.’”

The team injected small alpha-synuclein pre-formed polymers similar to those found in disease in the striatum region of the brain. “Our idea was if we put something in the striatum and there are connections going from the striatum into the substantia nigra region of the brain, would these alpha-synuclein polymers recruit additional alpha-synuclein found in the brain and travel through the neuro-anatomical connections into the substantia nigra and kill the neurons?”

The team’s conclusions challenge some previous assumptions with two key findings: One, the spread of the protein appears to not be restricted to neuronal cells but rather also involves supporting glial cells; and two, it doesn’t necessarily follow a precise anatomical route, said Todd Golde, M.D., Ph.D., executive director of the McKnight Brain Institute.

While the findings raise further questions, “Overall, it shows how pathology may spread throughout the brain is really complex and by understanding that, we may be able to find better ways to intervene,” Golde said. “This will help us to guide and focus therapy if we understand that it’s just not so simple. We need to understand this mechanism a lot better.”

Michelle Koidin Jaffee