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Researcher Q&A: Harald Sontheimer, PhD, Targets Memory Loss in Alzheimer’s

After 30 years, Harald Sontheimer, PhD, is as excited about his research as when be began.

"Discovering how things work never gets old," says Sontheimer, chair of neuroscience at UVA School of Medicine. "That's particularly true when it involves the human brain."

Specifically, researchers in the Sontheimer lab study ways to slow memory loss in diseases like Alzheimer's by reducing inflammation in the brain.

Their most promising target is an enzyme that triggers the breakdown of perineuronal nets that coat nerve cells. Inhibiting this enzyme may reduce the inflammation that contributes to memory loss.

Watch Sontheimer talk about his research and read his answers to our questions below.

What are you working on right now?

We are studying how specialized proteins and sugars that form a mesh-like coat around nerve cells, called perineuronal nets, can profoundly alter the signaling properties of nerve cells. Perineuronal nets can be broken down by enzymes that are released in the context of inflammation in neurodegenerative diseases such as Alzheimer's.

We recently discovered in mice bearing mutations that cause Alzheimer’s disease in humans that memory loss in the hippocampus is caused by a loss of perineuronal nets.  

What are the most intriguing potential clinical applications of your work?

If our findings hold up to further scrutiny, we may be able to delay certain forms of memory loss in Alzheimer's by preventing brain inflammation or, specifically, by inhibiting the enzymes that break apart perineuronal nets.

What recent discovery/paper/presentation has impacted the way you think?

My colleague, Bhanu Tewari, showed that malignant glial cells release enzymes that attach perineuronal nets around neurons and that this causes seizures. That piqued our interest in looking at the structures in other forms of epilepsy and Alzheimer's.  

What made you choose UVA Health as the place to do your research?

I came to UVA as chair of the Neuroscience Department. I was attracted to lead this team of incredible researchers due to a shared interest in neurodegenerative diseases and researching them from a unique perspective that considers brain inflammation as an important contributor to disease. 

What do you wish more people knew about your area of research?

Neuroscience is fun but can also be frustrating. The brain is so complicated, and with every discovery that neuroscientists make things get more complicated. I sometimes envy my colleagues who study simpler organs where we at least know how they work. Then again, neuroscience is always full of surprises and never gets boring.  

How did you become interested in your area of research?

My laboratory has been studying glial cells for over 30 years. Glial cells become reactive in disease states, and as part of this reactivity they release enzymes that digest molecules in the vicinity. We were initially interested in how glial cells may contribute to Alzheimer's and stumbled on these profound changes in perineuronal nets. 

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