Team Desjardins

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Neuro-immune Interactions | 2020

Role of PD-related Proteins as Drivers of Disease through Modulation of Innate and Adaptive Immunity

Study Rationale: The hallmark motor impairments in Parkinson’s disease patients are due to the progressive loss of a special type of neuron in the brain using the chemical messenger dopamine. The mechanisms leading to their destruction during disease progression are not well known. An emerging concept in the field of Parkinson’s disease is that the immune system plays a role in the progressive death of these neurons.

Hypothesis: Team Desjardins hypothesizes that Parkinson’s disease is initiated years before the emergence of motor dysfunction in response to mechanisms triggered following gut infection with Gram-negative bacteria. This leads to an autoimmune reaction producing specialized immune cells that can reach the brain and attack dopamine-producing neurons.

Study Design: Team Desjardins will study how mutations in proteins associated with Parkinson’s disease (PINK1, Parkin, LRRK2, VPS35, and GBA) affect the function of immune cells in isolated cell culture (in vitro), as well as in mouse models of Parkinson’s disease. In the model, the team will characterize how the immune system is stimulated during gut infection to produce cytotoxic T lymphocytes, and how these cells reach the brain and attack dopamine-producing neurons. Similar studies will also be done with immune cells from the blood of Parkinson’s disease patients and neurons derived from stem cells.

Impact on Diagnosis/Treatment of Parkinson’s Disease: The involvement of the immune system in Parkinson’s disease suggests that novel types of therapeutic approaches targeting immune cells could be developed to slow the progression of the disease or even prevent it early on before the emergence of motor impairments.

Leadership
Michel Desjardins, PhD
Coordinating Lead PI

Michel Desjardins, PhD

University of Montreal
Heidi McBride, PhD
Co-Investigator

Heidi McBride, PhD

McGill University
Jo Anne Stratton, PhD
Co-Investigator

Jo Anne Stratton, PhD

McGill University
Louis-Eric Trudeau, PhD
Co-Investigator

Louis-Eric Trudeau, PhD

University of Montreal
Samantha Gruenheld, PhD
CO-INVESTIGATOR

Samantha Gruenheld, PhD

McGill University
Lilia Rodriguez, PhD
Project Manager

Lilia Rodriguez, PhD

Université de Montréal

Project Outcomes

Team Desjardins' project will identify how alterations in the function of Parkinson’s disease-related proteins modulate the immune system and the pathological process leading to motor impairments, as well as key cellular processes that can be targeted for therapeutic intervention. View Team Outcomes.

Team Outputs

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Overall Contributions

Here is an overview of how this team’s article findings have contributed to the PD field as of November 2023. There are two different categorizations of these contributions – one by impact to the PD community and a second by scientific theme.

Impact

Theme

Featured Output

Below is an example of a research output from the team that contributes to the ASAP mission of accelerating discoveries for PD.

LRRK2 regulates the activation of the unfolded protein response and antigen presentation in macrophages during inflammation

A failure to regulate mitochondrial antigen presentation (MitAP) leads to the initiation of autoimmune mechanisms, which have been linked to motor impairment. Team Desjardins has further defined how MitAP is engaged during inflammation and has provided evidence that the PD-related protein, LRRK2, is involved in the regulation of this pathway. Previously, the Parkinson’s disease-related proteins PINK1 and Parkin were found to regulate the MitAP system, suggesting that PD proteins are regulators of the immune response and carry out some of this regulation by acting along a common pathway.

Team Accolades

Members of the team have been recognized for their contributions.

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