Chen
From cancer associations to altered immunity in the pathogenesis of Parkinson’s disease
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Neuro-Immune Interactions
Before the ASAP initiative, growing evidence suggested the immune system’s involvement in Parkinson’s disease (PD). Despite advancements in the field, the community lacked a clear understanding of the mechanisms connecting the immune system to (PD), whether immune changes are a cause or consequence of the disease, and the role of the innate and adaptive immune responses in PD progression. Teams within the Neuro-Immune Interactions theme are investigating the roles of immune cells in both the central nervous system and the periphery for PD development and progression.
Highlights
View AllMetagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms
To investigate the role of gut microbiome in Parkinson’s disease, Team Liddle conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from start to end. Here Team Liddle shows that over 30% of species, genes and pathways tested have altered abundances in PD, depicting a widespread dysbiosis.
Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease
Dopaminergic cell loss due to the accumulation of α-syn is a core feature of the pathogenesis of Parkinson disease. Neuroinflammation specifically induced by α-synuclein has been shown to exacerbate neurodegeneration, yet the role of central nervous system (CNS) resident macrophages in this process remains unclear. Team Sulzer found that a specific subset of CNS resident macrophages, border-associated macrophages (BAMs), play an essential role in mediating α-synuclein related neuroinflammation.
Integrated Multi-Cohort Analysis of the Parkinson's Disease Gut Metagenome
The gut microbiome is altered in several neurologic disorders, including Parkinson's disease (PD). Here, Team Gradinaru profiled the metagenome in PD for alterations in microbial features. The findings from this study showed consistent and novel alterations in metabolic potential and microbial gene abundance in individuals with PD.
LRRK2 regulates the activation of the unfolded protein response and antigen presentation in macrophages during inflammation
While the contribution of inflammation in the pathological process leading to Parkinson’s disease (PD) is well established, a growing body of evidence supports a role for the long-lasting adaptive immune system in the disease. Team Desjardins showed that, in inflammatory conditions, the PD-proteins PINK1 and Parkin negatively regulate the presentation of mitochondrial antigens on MHC I molecules, a process referred to as MitAP (Mitochondrial Antigen Presentation).
Our Teams
The focus across these teams will be to uncover the molecular and cellular contributions of the neuro-immune system in Parkinson’s disease.
Desjardins
The role of PD-related proteins as drivers of disease through modulation of innate and adaptive immunity
Hafler
Tracing the Origin and Progression of Parkinson’s Disease through the Neuro-Immune Interactome
Jakobsson
Activation of transposable elements as a trigger of neuroinflammation in Parkinson’s disease
Kordower
Co-Pathologies Drive Neuroinflammation and Progression in PD
Schapira
The genome-microbiome axis in the cause of Parkinson disease: Mechanistic insights and therapeutic implications from experimental models and a genetically stratified patient population.
Sulzer
Adaptive immunity in the etiology and progression of Parkinson’s disease
