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Neurosci Lett. 2014 Sep 5;579:35-40. doi: 10.1016/j.neulet.2014.07.014. Epub 2014 Jul 17.

Neuroprotection by Orexin-A via HIF-1α induction in a cellular model of Parkinson's disease.

Author information

1
Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR China.
2
Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, PR China.
3
Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
4
Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
5
Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: Tpan1@mdanderson.org.
6
Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR China. Electronic address: yunchw@medmail.com.cn.

Abstract

Orexin-A, a neuropeptide secreted by hypothalamic neurons, may be neuroprotective in many neurological conditions such as cerebral ischaemia. One mechanism postulated to be involved in the neuroprotection by Orexin-A is the induction of hypoxia inducible factor 1 alpha (HIF-1α). Parkinson's disease (PD) is a progressive neurodegenerative disorder and mitochondrial dysfunction has been demonstrated to play a role in its pathogenesis. Mitochondrial dysfunction may cause reduction of O2 consumption and subsequently activate prolyl hydroxylase, which leads to decreased level of HIF-1α. In this study, we used MPP(+)-treated SH-SY5Y cells as an in vitro cellular model of PD to test the role of Orexin-A as an inducer of HIF-1α. Our results showed that Orexin-A not only induced HIF-1α but also activated downstream targets of HIF-1α, such as vascular endothelial growth factor and erythropoietin. Thus, Orexin-A treatment attenuated MPP(+)-induced cell injury and this effect was blocked when HIF-1α was suppressed. Hence, we conclude that induction of HIF-1α is one of the mechanisms involved in the neuroprotection by Orexin-A.

KEYWORDS:

Dopaminergic neuron; HIF-1α; Neurodegenerative disease; Neuroprotection; Orexin-A; Parkinson's disease

PMID:
25038418
DOI:
10.1016/j.neulet.2014.07.014
[Indexed for MEDLINE]

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