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Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo

Title
Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo
Authors
Leem, EunjuKim, Hyung-JunChoi, MinjiKim, SehwanOh, Yong SeokLee, Kea JooChoe, Young-ShikUm, Jae-YoungShin, Won-HoJeong, Jae YeongJin, Byung KwanKim, Dong WoonMcLean, CatrionaFisher, Paul BKholodilov, NikolaiAhn, Kwang SeokLee, Jae ManJung, Un JuLee, Seok-GeunKim, Sang Ryong
DGIST Authors
Oh, Yong Seok
Issue Date
2018-04
Citation
Cell Death and Disease, 9(5)
Type
Article
Article Type
Article
Keywords
rapid subtraction hybridizationparkinsons-disease modelspkc-deltaautophagyapoptosispathwayneurodegenerationdegenerationtransductionexpression
ISSN
2041-4889
Abstract
The role of astrocyte elevated gene-1 (AEG-1) in nigral dopaminergic (DA) neurons has not been studied. Here we report that the expression of AEG-1 was significantly lower in DA neurons in the postmortem substantia nigra of patients with Parkinson's disease (PD) compared to age-matched controls. Similarly, decreased AEG-1 levels were found in the 6-hydroxydopamine (6-OHDA) mouse model of PD. An adeno-associated virus-induced increase in the expression of AEG-1 attenuated the 6-OHDA-triggered apoptotic death of nigral DA neurons. Moreover, the neuroprotection conferred by the AEG-1 upregulation significantly intensified the neurorestorative effects of the constitutively active ras homolog enriched in the brain [Rheb(S16H)]. Collectively, these results demonstrated that the sustained level of AEG-1 as an important anti-apoptotic factor in nigral DA neurons might potentiate the therapeutic effects of treatments, such as Rheb(S16H) administration, on the degeneration of the DA pathway that characterizes PD. © 2018 The Author(s).
URI
http://hdl.handle.net/20.500.11750/6293
DOI
10.1038/s41419-018-0491-3
Publisher
Nature Publishing Group
Related Researcher
  • Author Oh, Yong-Seok Molecular Psychiatry Lab
  • Research Interests Monoaminergic regulation of the CNS and mood;anxiety disorder; 모노아민 (세로토닌, 도파민)에 의한 신경조절과 기분;불안 장애 기전 연구
Files:
Collection:
Department of Brain and Cognitive SciencesMolecular Psychiatry Lab1. Journal Articles


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