Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review)

Jeon,Min‑Tae; Kim,Sang  Ryong

doi:10.3892/br.2014.397

Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review)

Authors:
- Min‑Tae Jeon
- Sang Ryong Kim
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Affiliations: School of Life Sciences, Kyungpook National University, Daegu 702‑701, Republic of Korea
Published online on: December 9, 2014 https://doi.org/10.3892/br.2014.397
Pages: 137-140

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Abstract

Although there are ongoing intensive research efforts, no effective pharmacological therapies for Parkinson's disease (PD) have been developed thus far. However, with the development of efficient gene delivery systems, gene therapy for PD has become a focus of research and increasing evidence suggests that continuous production of neurotrophic factors play a significant role in the functional restoration of the nigrostriatal dopaminergic (DA) system. Our recent study reported that the transduction of DA neurons with ras homolog enriched in brain, which has an S16H mutation [Rheb(S16H)], protected the nigrostriatal DA projection in a neurotoxin model of PD in vivo. In addition, Rheb(S16H) expression significantly increased the levels of glial cell line‑derived neurotrophic factor and brain‑derived neurotrophic factor, which contributed to the neuroprotective effects of Rheb(S16H) in DA neurons in the adult brain, indicating that the activation of the signaling pathways involved in cell survival by a specific gene delivery, such as Rheb(S16H) to adult neurons, may be a useful strategy to protect neural systems in the adult brain. In the present study, a brief overview of our recent studies is provided, which demonstrates the neuroprotective mechanisms of Rheb(S16H) on the nigrostriatal DA projection in the adult brain.

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