Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo
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Date
2018-04-18Source Title
Cell Death and DiseasePublisher
NATURE PUBLISHING GROUPAffiliation
Florey Department of Neuroscience and Mental HealthMetadata
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Journal ArticleCitations
Leem, E., Kim, H. -J., Choi, M., Kim, S., Oh, Y. -S., Lee, K. J., Choe, Y. -S., Um, J. -Y., Shin, W. -H., Jeong, J. Y., Jin, B. K., Kim, D. W., McLean, C., Fisher, P. B., Kholodilov, N., Ahn, K. S., Lee, J. M., Jung, U. J., Lee, S. -G. & Kim, S. R. (2018). Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo. CELL DEATH & DISEASE, 9 (5), https://doi.org/10.1038/s41419-018-0491-3.Access Status
Open AccessAbstract
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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