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Cell Death Dis. 2018 May 1;9(5):449. doi: 10.1038/s41419-018-0491-3.

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

Author information

1
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Institute of Life Science & Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea.
2
Department of Neural Development and Disease, Department of Structure & Function of Neural Network, Korea Brain Research Institute, Daegu, 41062, Republic of Korea.
3
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
4
Department of Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and Technology, Daegu, 42988, Republic of Korea.
5
Predictive Model Research Center, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.
6
Department of Biochemisry and Molecular Biology, Department of Neuroscience Graduate School, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
7
Department of Anatomy, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.
8
Victorian Brain Bank Network, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, 3004, Australia.
9
Department of Anatomical Pathology, Alfred Hospital, Melbourne, VIC, 3004, Australia.
10
Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
11
Department of Neurology, Columbia University, New York, NY, 10032, USA.
12
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.
13
Department of Food Science and Nutrition, Pukyong National University, Busan, 48513, Republic of Korea.
14
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea. seokgeun@khu.ac.kr.
15
KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, 02447, Republic of Korea. seokgeun@khu.ac.kr.
16
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Institute of Life Science & Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea. srk75@knu.ac.kr.
17
Brain Science and Engineering Institute, Kyungpook National University, Daegu, 41944, Republic of Korea. srk75@knu.ac.kr.

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.

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