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Protection of nigral dopaminergic neurons by AAV1 transduction with Rheb(S16H) against neurotoxic inflammation in vivo

Title
Protection of nigral dopaminergic neurons by AAV1 transduction with Rheb(S16H) against neurotoxic inflammation in vivo
Authors
Kim, SehwanMoon, Gyeong JoonOh, Yong-SeokPark, JunghaShin, Won-HoJeong, Jae YeongChoi, Kwang ShikJin, Byung KwanKholodilov, NikolaiBurke, Robert EKim, Hyung-JunHa, Chang ManLee, Seok-GeunKim, Sang Ryong
DGIST Authors
Oh, Yong-Seok
Issue Date
2018-02
Citation
Experimental and Molecular Medicine, 50(2), e440
Type
Article
Article Type
Article
Keywords
Parkinsons-Disease BrainSubstantia-NigraNeurotrophic FactorMicroglial ActivationProthrombin Kringle-2BdnfModelMechanismsGdnfNeurodegeneration
ISSN
1226-3613
Abstract
We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson's disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2). Our observations showed that Rheb(S16H) transduction played a role in the neuroprotection of the nigrostriatal DA system against pKr-2-induced neurotoxic inflammation, even though there were similar levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta), in the AAV1-Rheb(S16H)-treated substantia nigra (SN) compared to the SN treated with pKr-2 alone; the neuroprotective effects may be mediated by the activation of neurotrophic signaling pathways following Rheb(S16H) transduction of nigral DA neurons. We conclude that AAV1-Rheb(S16H) transduction of neuronal populations to activate the production of neurotrophic factors and intracellular neurotrophic signaling pathways may offer promise for protecting adult neurons from extracellular neurotoxic inflammation.
URI
http://hdl.handle.net/20.500.11750/6219
DOI
10.1038/emm.2017.261
Publisher
NLM (Medline)
Related Researcher
  • Author Oh, Yong-Seok Molecular Psychiatry Lab
  • Research Interests Monoaminergic regulation of the CNS and mood;anxiety disorder; 모노아민 (세로토닌, 도파민)에 의한 신경조절과 기분;불안 장애 기전 연구
Files:
Collection:
Department of Brain and Cognitive SciencesMolecular Psychiatry Lab1. Journal Articles


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