Journal
NEUROBIOLOGY OF DISEASE
Volume 169, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2022.105724
Keywords
LRRK2; Parkinson ?s disease; Immune system; Inflammation; Kinase inhibitors; Biomarkers
Categories
Funding
- Michael J Fox Foundation
- Italian Ministry of Research MUR
- CARIPLO Foundation [2016-0428]
- Italian Ministry of Health [GR-2016-02362548]
- Regional Foundation for Biomedical Research [1737591]
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This review summarizes the role of LRRK2 in modulating central and peripheral inflammation in Parkinson's disease and inflammatory disease models. In addition, it discusses the potential benefits of LRRK2 inhibitors and anti-inflammatory drugs in reducing disease risk and progression.
Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene are associated with familial and sporadic cases of Parkinson's disease (PD) but are also found in patients with immune- related disorders, such as inflammatory bowel disease (IBD) and leprosy, linking LRRK2 to the immune system. Supporting this genetic evidence, in the last decade LRRK2 was robustly shown to modulate inflammatory responses at both systemic and central nervous system level. In this review, we recapitulate the role of LRRK2 in central and peripheral inflammation in PD and inflammatory disease models. Moreover, we discuss how LRRK2 inhibitors and anti- inflammatory drugs may be beneficial at reducing disease risk/progression in LRRK2-mutation carriers and manifesting PD patients, thus supporting LRRK2 as a promising disease-modifying PD strategy.
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