Grants Support Researching Role of Non-neuronal Cell Types

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by Patricia Inácio, PhD |

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Scientists at the Duke University School of Medicine have received two grants totaling $18 million to investigate how different cells in the brain and in the gut may foster the onset and progression of Parkinson’s disease.

The grants from the Aligning Science Across Parkinson’s (ASAP) initiative will fund two projects, both part of ASAP’s Collaborative Research Network  for Parkinson’s. One will be led by Nicole Calakos, MD, PhD, who is the Lincoln Financial Group distinguished professor of neurobiology and neurology, and the other by Rodger Liddle, MD, professor of medicine at the North Carolina school.

“This is an exciting moment for Duke, and an exciting moment for anyone with or affected by Parkinson’s disease,” Calakos said in a Duke press release.

“Duke has been invested in Parkinson’s for a long time, but this funding launches a new era because of the depth and diversity of new opportunities we will have to understand, fight, and prevent this insidious disease,” Calakos said.

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Parkinson’s disease is characterized by the loss of neurons, or nerve cells, that produce the neurotransmitter dopamine — a chemical messenger essential for muscle control — due to the accumulation of toxic clumps, called Lewy bodies. These are composed mainly of alpha-synuclein protein aggregates.

A good deal of research has focused on the dopamine-producing neurons, but these cells do not live isolated in the brain; they are in close proximity with other cell types.

Calakos’ team project will investigate how the death of dopamine-producing neurons is modulated by the connections they make with neighboring cells in the brain. Their hypothesis is that cells that closely communicate with and support the dopamine-producing neurons also may be important. So,  targeting these cells — and not dopamine neurons alone — may help lessen the disease.

In turn, the project by Liddle’s team will investigate the potential role of specialized cells in the gut – called enteroendocrine cells – in the onset of Parkinson’s disease.

Enteroendocrine cells produce and release hormones in response to a number of stimuli. A body of research supports a connection between the brain and the gut — called the brain-gut axis — and that Parkinson’s might be triggered in the gut and subsequently spread to the brain.

Liddle’s team will investigate whether the toxic forms of alpha-synuclein that compose the Lewy bodies derive from the enteroendocrine cells and reach the brain through the brain-gut axis. The outcomes of this research may identify enteroendocrine cells as a potential target for future therapies.

“Enteroendocrine cells provide a potential pathway for corrupted alpha-synuclein all the way from the intestine through the vagus nerve directly into the brain,” Liddle said. “This knowledge gives us real insights into Parkinson’s disease — and may act as the foundation for designing therapies to treat Parkinson’s and other conditions caused by altered gut-brain signaling.”

The ASAP Collaborative Research Network, launched in 2019, was designed to bring together researchers across multiple disciplines, institutions, career stages, and geographies, in a global effort to tackle the mechanisms driving Parkinson’s development and progression.

The Michael J. Fox Foundation for Parkinson’s Research is ASAP’s partner in implementing these grants.

“Each team selected for the Collaborative Research Network brings unique expertise and perspective to ASAP’s mission of tackling key knowledge gaps in disease understanding through open science,” said Ekemini Riley, PhD, ASAP managing director.

“We are proud to partner with Duke University on these innovative and impactful projects that will position the field closer to new treatments for the millions living with and at risk of Parkinson’s disease,” Riley said.

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