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Parkin mediates neuroprotection through activation of Notch1 signaling

Yoon, Ji-Hye; Ann, Eun-Jung; Kim, Mi-Yeon; Ahn, Ji-Seon; Jo, Eun-Hye; Lee, Hye-Jin; Lee, Hye-Won; Lee, Young Chul; Kim, Jeong-Sun; Park, Hee-Sae

doi: 10.1097/WNR.0000000000000726
Cellular, Molecular and Developmental Neuroscience

Parkin, an E3 ubiquitin ligase, is the most frequently mutated gene in hereditary Parkinson’s disease. Inactivation of Parkin leads to impairment of the ubiquitin–proteasome system, resulting in the accumulation of misfolded or aggregated proteins and ensuing neurodegeneration. In this study, we show that Parkin positively regulates the Notch1 signaling pathway. Overexpression of Parkin stabilized Notch1-IC protein levels, whereas knockdown of Parkin decreased Notch1-IC protein stability. Notably, overexpression of Parkin disrupted oxidative stress-induced apoptosis in neuronal cells. However, knockdown of Notch1 inhibited Parkin-induced neuronal cell survival. Together, these results indicate that Parkin is a novel regulator of the Notch1 signaling pathway, which promotes neuronal cell survival.

aSchool of Biological Sciences and Technology, Hormone Research Center

bDepartment of Chemistry and Institute of Basic Sciences, Chonnam National University, Gwangju, Republic of Korea

Correspondence to Hee-Sae Park, PhD, School of Biological Sciences and Technology, Chonnam National University, Yongbong-dong, Buk-ku, Gwangju 500-757, Republic of Korea Tel: +82 62 530 2197; fax: +82 62 530 2199; e-mail:

Received September 29, 2016

Accepted December 1, 2016

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