Professor Daewoo Lee awarded NIH grant to study how pathogenic protein spreads in Parkinson's disease and Lewy body dementia

Biologist Daewoo Lee received a two-year $403,000 grant from the National Institutes of Health to probe how a pathogenic protein is able to spread from cell to cell in the brain, leading to progression of neurodegenerative diseases such as Parkinson's disease and Lewy body dementia.

"The intriguing concept of prion-like spreading of pathogenic proteins has emerged in recent years, with the potential to transform neurodegeneration research by uncovering potential therapeutic targets for slowing or even halting the progression of dementia pathology," said Lee, professor of biological sciences in the College of Arts & Sciences.

The neuronal protein alpha-synuclein is found throughout the body, but when the pathogenic protein leads to the abnormal accumulation of protein aggregates called Lewy bodies, these neurodegenerative diseases occur and progress.

Since Parkinson's disease risk factors such as traumatic brain injury and sleep deprivation increase neuronal activity and extracellular levels of alpha-synuclein, Lee and his lab are especially interested in activity-dependent release of alpha-synuclein. Hyperexcitability and seizures also are known to be associated with pathological progression of Lewy body dementia. Lee also is interested in how mutations of alpha-synuclein and other genetic factors affect this activity-dependent release.

Lee notes there are just two studies on activity-dependent alpha-synuclein release so far. His lab will be using fruit fly larva as an in vivo model to potentially reveal the molecular underpinnings of this protein activity in his study of activity-dependent release of human alpha-synuclein.

"The fruit fly Drosophila melanogaster has a whole variety of sophisticated genetic approaches and its well-established neuromuscular junction is an excellent model to study human disease because gene sequence and function are highly conserved between flies, rats, and humans," he said.

The innovation in his research comes in using powerful genetic methodologies such as optogenetics (controlling the neuronal activity with light) along with readily available transgenic lines and genetic tools such as archived mutant and RNA interference lines.

"We strongly believe that this novel research methodology, once developed, has great potential for addressing critical unanswered questions relating to the mechanisms of prion-like transmission and will have broad impact," Lee said.