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Cell Death and Disease
년도 2018
학술지명 Cell Death and Disease
논문명 Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo
게재권/집 vol.9/ no.5 / Article number 449
수록페이지
저자명 Leem Eunju, Kim Hyung-Jun, Choi Minji, Kim Sehwan, Oh Yong Seok, Lee Kea Joo, Choe Young-Shik, Um Jae-Young, Shin Won-Ho, Jeong Jae Yeong, Jin Byung Kwan, Kim Dong Woon, McLean Catriona, Fisher Paul B, Kholodilov Nikolai, Ahn Kwang Seok, Lee Jae Man, Jung
Link 관련링크 https://www.nature.com/articles/s41419-018-0491-3 5236회 연결
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.