LRRK2 at the Interface Between Peripheral and Central Immune Function in Parkinson's.
Rebecca L Wallings1, Mary K Herrick1,2, Malú Gámez Tansey1
1Department of Neuroscience and Center for Translational Research in Neurodegenerative Disease, University of Florida College of Medicine, Gainesville, FL, United States.
Frontiers in Neuroscience
|June 9, 2020
Summary
Parkinson's disease (PD) involves immune responses and neuroinflammation. Leucine-rich-repeat kinase 2 (LRRK2) mutations link PD to immune disorders and infections, suggesting LRRK2’s role in regulating peripheral immunity and neuroinflammation.
Area of Science:
- Neuroimmunology
- Genetics of Neurodegenerative Diseases
Background:
- Parkinson's disease (PD) pathophysiology involves interplay between peripheral immunity and neuroinflammation.
- Mutations in leucine-rich-repeat kinase 2 (LRRK2) are linked to PD, inflammatory bowel disease (IBD), and bacterial infections.
- LRRK2 plays a role in regulating the immune system both centrally (CNS) and peripherally.
Purpose of the Study:
- To review evidence supporting the role of peripheral immune signaling in neurodegeneration in PD.
- To explore the hypothesis that LRRK2 bridges peripheral immunity and neuroinflammation in PD pathogenesis.
- To provide rationale for LRRK2's central role at the intersection of immune responses and neuroinflammation.
Main Methods:
- Literature review of current research on LRRK2, PD, and immune system interactions.
- Analysis of genetic associations between LRRK2 mutations and immune-related disorders.
- Synthesis of evidence linking peripheral immune signaling to neuroinflammation in PD models.
Main Results:
- LRRK2 mutations are associated with PD and various immune-related conditions.
- LRRK2 is functionally implicated in both central and peripheral immune regulation.
- Evidence suggests peripheral immune responses modulate neurodegeneration in PD, including LRRK2-associated forms.
Conclusions:
- Peripheral immune signaling is a critical factor in PD neurodegeneration.
- LRRK2 is positioned at the interface of peripheral immunity and neuroinflammation.
- Further research into LRRK2's immune functions could reveal novel therapeutic targets for PD.
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