Brain Hepcidin Suppresses Major Pathologies in Experimental Parkinsonism

• Main Authors: Tuo Liang, Zhong-Ming Qian, Ming-Dao Mu, Wing-Ho Yung, Ya Ke
• Format: Article
• Language: English
• Published: Elsevier 2020-07-01
• Series: iScience
• Subjects: Molecular Biology; Neuroscience; Cell Biology
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004220304715

Summary: Despite intensive research on Parkinson disease (PD) for decades, this common neurodegenerative disease remains incurable. We hypothesize that abnormal iron accumulation is a common thread underlying the emergence of the hallmarks of PD, namely mitochondrial dysfunction and α-synuclein accumulation. We investigated the powerful action of the main iron regulator hepcidin in the brain. In both the rotenone and 6-hydroxydopamine models of PD, overexpression of hepcidin by means of a virus-based strategy prevented dopamine neuronal loss and suppressed major pathologies of Parkinsonism as well as motor deficits. Hepcidin protected rotenone-induced mitochondrial deficits by reducing cellular and mitochondrial iron accumulation. In addition, hepcidin decreased α-synuclein accumulation and promoted clearance of α-synuclein through decreasing iron content that leads to activation of autophagy. Our results not only pinpoint a critical role of iron-overload in the pathogenesis of PD but also demonstrate that targeting brain iron levels through hepcidin is a promising therapeutic direction.