23 June 2022
Peripheral inflammation implicated in Parkinson’s disease
Published online 4 April 2018
Researchers shed light on how a mutated gene mediates brain degeneration typically associated with Parkinson's disease.
A new study reveals a surprising role for LRRK2 gene mutations, which are implicated in Parkinson’s disease (PD) and account for 40% of familial PD cases among North African Arabs1.
Both genetic predispositions and environmental factors act in concert to develop the neurological disorder where nerve cells in specific areas of the brain undergo degeneration. Previously, scientists had difficulty dismantling the exact mechanisms by which LRRK2 contributes to PD development. Now, a new study in Brain2 is offering some answers.
During testing, the scientists induced a systemic inflammation that mimics a bacterial infection in mice carrying the most common mutant form of the human LRRK2 gene. The induction stimulated the peripheral immune cells that reside outside the brain, and in turn, secreted signals that caused inflammation of the nerve cells.
This process resulted in the degeneration of said nerve cells, a feature that typically characterizes PD.
“The key question for us was whether LRRK2 mutations directly mediate neuroinflammation via the brain’s resident immune cells, microglia, and/or invading T immune cells," says leading author, Elena Kozina from the Department of Neurosciences at Thomas Jefferson University, USA.
"It turns out, however, that microglia do not express LRRK2, nor do T cells that infiltrate the brain. This lead us to think that neuroinflammation is likely triggered by altered peripheral immune signaling,” adds Kozina.
These results provide, for the first time, an insight into how frequent LRRK2 mutations can mediate the development of Parkinson’s.
- Lesage, S. et al. LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N. Engl. J. Med. 354, 422–423 (2006).
- Kozina E. et al. Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo. Brain https://doi.org/10.1093/brain/awy077 (2018).