iScience
Volume 23, Issue 7, 24 July 2020, 101284
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Article
Brain Hepcidin Suppresses Major Pathologies in Experimental Parkinsonism

https://doi.org/10.1016/j.isci.2020.101284Get rights and content
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Highlights

  • Hepcidin rescues motor deficits and dopaminergic neurodegeneration in PD models

  • Hepcidin represses iron accumulation and mitochondrial deficits in Parkinsonism

  • Hepcidin promotes clearance of α-synuclein via autophagy activation in PD model

  • Manipulating brain hepcidin level has potential application in treating PD

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.

Subject Areas

Molecular Biology
Neuroscience
Cell Biology

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