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Molecular Brain
Published in: Molecular Brain 1/2016

Open Access 01-12-2016 | Research

Down-regulation of p21-activated serine/threonine kinase 1 is involved in loss of mesencephalic dopamine neurons

Authors: Hwanhee Kim, Jun-Young Oh, Sun-Lim Choi, Yeon-Ju Nam, Anna Jo, Ara Kwon, Eun-Young Shin, Eung-Gook Kim, Hyong Kyu Kim

Published in: Molecular Brain | Issue 1/2016

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Abstract

Background

Although the roles of p21-activated serine/threonine kinase 1 (PAK1) have been reported in some neurodegenerative diseases, details regarding neurodegeneration are still limited. Hence, we tried to determine the role of PAK1 and molecular mechanisms of neuronal death involved in neurodegeneration.

Results

Expression of a dominant-negative form of PAK1 (PAK1H83,86L, K299R, PAK1-DN) decreased the cell viability and increased cell death induced by oxidative stress. Indeed, oxidative stress decreased the phosphorylation of PAK1 in neuroblastoma cells, cultured dopamine (DA) neurons, or rat midbrains. PAK1-DN reduced the level of Bcl-2 protein, through an ubiquitin/proteasome-dependent mechanism. The level of Bcl-2 may be regulated by PAK1-ERK signaling and/or PAK1, directly. Conversely, expression of an active form of PAK1 (PAK1T423E, PAK1-CA) could recover both loss of DA neurons in the substantia nigra (SN) and behavioral defects in a 6-OHDA-induced hemiparkinsonian rat model.

Conclusions

Our data suggest that the oxidative stress-induced down-regulation of PAK1 activity could be involved in the loss of mesencephalic DA neurons through modulation of neuronal death, suggesting a novel role of PAK1 as a molecular determinant and mechanisms in the pathogenesis of Parkinson’s disease.
Appendix
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Metadata
Title
Down-regulation of p21-activated serine/threonine kinase 1 is involved in loss of mesencephalic dopamine neurons
Authors
Hwanhee Kim
Jun-Young Oh
Sun-Lim Choi
Yeon-Ju Nam
Anna Jo
Ara Kwon
Eun-Young Shin
Eung-Gook Kim
Hyong Kyu Kim
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Molecular Brain / Issue 1/2016
Electronic ISSN: 1756-6606
DOI
https://doi.org/10.1186/s13041-016-0230-6

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