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 AllA single Citrobacter rodentium infection in Pink1 knockout and wild type mice leads to regional blood-brain-barrier perturbation and limited microglial activation without dopamine neuron axon terminal loss
Research suggests immune system activation may contribute to Parkinson’s disease development. Mild infections can increase BBB permeability, triggering brain inflammation in genetically susceptible individuals, potentially leading to PD pathology.
STING dampens the unfolded protein response to enable the presentation of self antigens on MHC-I during inflammation
STING pathway regulates antigen presentation through the UPR, impacting immune response in PD and autoimmune diseases. Targeting STING and UPR could be therapeutic.
An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death
We examined the impact of mutant LRRK2-G2019S on iron homeostasis within a model macrophage cell line. Results revealed a dysregulation of iron-related proteins in steady state and a complete block in the degradation of the ferritinophagy NCOA4.
Cell-autonomous and non-cell-autonomous drivers of dopamine neuron vulnerability in Parkinson’s disease
This review examines evidence for cell-autonomous mechanisms and non-cell-autonomous processes arising from glial and peripheral immune cells and how these pathways can converge to create chronic cellular stress and trigger cell death mechanisms.
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
