An Orally Active Pharmacological Inhibitor Of Complement C5a Signalling Protects Against Dopaminergic Degeneration In Experimental Parkinson's Disease

Autor: Richard D. Gordon, Kiane Zhou, Trent M. Woodruff, Vinod Kumar, Ashoka Garin-Michaud, Susanna Mantovani, Anumantha G. Kanthasamy
Rok vydání: 2015
Předmět:
Zdroj: The FASEB Journal. 29
ISSN: 1530-6860
0892-6638
Popis: Parkinson's disease (PD) is the most common neurodegenerative movement disorder and imposes a severe socioeconomic burden on ageing populations. The pathological hallmark of PD is a progressive loss of dopaminergic neurons in the midbrain that manifests as a range of debilitating motor and non-motor symptoms. The chronic neuroinflammatory response that accompanies dopaminergic degeneration is known to drive disease progression. Activation of the innate immune complement system has been reported in PD patients, with early complement fragments upregulated in the nigrostriatal system. Given the potent inflammatory activity of the complement anaphylatoxin C5a, we hypothesized that microglial C5aR signalling could drive neuroinflammation in PD brains and exacerbate disease pathology. In this study, we demonstrate elevated C5a levels in serum and CSF samples from PD patients, suggesting widespread complement activation in PD. We also found that synuclein aggregates can activate the complement cascade to generat...
Databáze: OpenAIRE
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