Open AccessRoles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo
Author(s) -
MinTae Jeon,
Sang Ryong Kim
Publication year - 2014
Publication title -
biomedical reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.607
H-Index - 25
eISSN - 2049-9442
pISSN - 2049-9434
DOI - 10.3892/br.2014.397
Subject(s) - pars compacta , substantia nigra , rheb , neuroscience , neurotrophic factors , neuroprotection , glial cell line derived neurotrophic factor , biology , dopaminergic , dopamine , signal transduction , microbiology and biotechnology , genetics , receptor , pi3k/akt/mtor pathway , mtorc1
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.