The abberrant accumulation of the protein α-synuclein occurs in most cases of Alzheimer's disease, and defines pathology in dementia with Lewy bodies and Parkinson's disease. We know that the majority of riskfor these diseases is not genetically inherited, but comes from environmental factors along with aging. However, what these environmental factors consist of that interact in the aging process is mostly an open question.

Through a series of screens, we identified environmentally-relevant concentrations of nanoplastics that are able to soak into neurons and interact with α-synuclein at the lysosome. The interaction between nanoplastics and α-synuclein does not appear to be benign: nanoplastics re-arrange the molecular structure of α-synuclein into a conformation that looks like the type of folding associated with pathological spread in different dementias and Parkinson's disease. 

Questions remain about gut and brain exposures to nanoplastics in dementia risk, why types of nanoplastic particles pose the greatest risk, and what we can do to counteract these interactions once they have begun.

Our recent published work in this nascent area has been the subject of 72 news stories from outlets across the world. 

<A post-doctoral position is now open to study neuroinflammation mechanisms in PD!*>

*email parkinson.lab@duke.edu to apply!

Mutations in the gene that encodes the protein known as LRRK2 are among the most common known genetic causes of neurodegeneration and Parkinson's disease. Mutations that cause neurodegeneration appear to increase LRRK2 activity. Usually genetic variation linked with neurodegeneration results in loss of function, but the gain of function in LRRK2 presents a rare oppurtunity to peer into the inner workings of this novel enzymatic cascade.

Through recent single-cell sequencing datasets, we now understand that some of the highest LRRK2 expression levels are in peripheral immune cells in the innate immune system. 

In our long-standing program initiated over a decade ago, we continue to closely examine LRRK2 function in immune cells. We utilize a series of different biochemical approaches to probe the inner catalytic core of LRRK2 enzymatic cycling in macrophages cells where LRRK2 expression is very high. disease-relevant cells. In a novel hypothesis we are testing experimentally, we propose that LRRK2-expressing immune cells that invade the brain from the periphery critically mediate the overt loss of neurons in the course of disease, contributing to disease phenotypes in a non-cell autonomous manner. 

If we can better understand the nature of how LRRK2 activity can cause Parkinson's disease, we might be better able to develop new therapies that block the disease from moving forward.

We are following our recent published observations into potential interventions in different models of dementia and Parkinson's disease.