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Brain Hepcidin Suppresses Major Pathologies in Experimental Parkinsonism.


ABSTRACT: 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 ?-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 ?-synuclein accumulation and promoted clearance of ?-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.

SUBMITTER: Liang T 

PROVIDER: S-EPMC7334576 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Brain Hepcidin Suppresses Major Pathologies in Experimental Parkinsonism.

Liang Tuo T   Qian Zhong-Ming ZM   Mu Ming-Dao MD   Yung Wing-Ho WH   Ke Ya Y  

iScience 20200619 7


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 str  ...[more]

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