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Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein

 Eunna Chung  ;  Youngsil Choi  ;  Jiae Park  ;  Wonheum Nah  ;  Jaehyung Park  ;  Yukdong Jung  ;  Joonno Lee  ;  Hyunji Lee  ;  Soyoung Park  ;  Sunyoung Hwang  ;  Seongcheol Kim  ;  Jongseok Lee  ;  Dongjae Min  ;  Junghwan Jo  ;  Shinyoung Kang  ;  Minyong Jung  ;  Phil Hyu Lee  ;  H Earl Ruley  ;  Daewoong Jo 
 SCIENCE ADVANCES, Vol.6(18) : eaba1193, 2020-04 
Journal Title
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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by mitochondrial dysfunction, Lewy body formation, and loss of dopaminergic neurons. Parkin, an E3 ubiquitin ligase, is thought to inhibit PD progression by removing damaged mitochondria and suppressing the accumulation of α-synuclein and other protein aggregates. The present study describes a protein-based therapy for PD enabled by the development of a cell-permeable Parkin protein (iCP-Parkin) with enhanced solubility and optimized intracellular delivery. iCP-Parkin recovered damaged mitochondria by promoting mitophagy and mitochondrial biogenesis and suppressed toxic accumulations of α-synuclein in cells and animals. Last, iCP-Parkin prevented and reversed declines in tyrosine hydroxylase and dopamine expression concomitant with improved motor function induced by mitochondrial poisons or enforced α-synuclein expression. These results point to common, therapeutically tractable features in PD pathophysiology, and suggest that motor deficits in PD may be reversed, thus providing opportunities for therapeutic intervention after the onset of motor symptoms.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
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