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Upregulation of Neuronal Rheb(S16H) for Hippocampal Protection in the Adult Brain

by Gyeong Joon Moon 1,†, Minsang Shin 2,3,† and Sang Ryong Kim 1,2,*
1
BK21 plus KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Korea
2
Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Korea
3
Department of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(6), 2023; https://doi.org/10.3390/ijms21062023
Received: 18 February 2020 / Revised: 14 March 2020 / Accepted: 16 March 2020 / Published: 16 March 2020
Ras homolog protein enriched in brain (Rheb) is a key activator of mammalian target of rapamycin complex 1 (mTORC1). The activation of mTORC1 by Rheb is associated with various processes such as protein synthesis, neuronal growth, differentiation, axonal regeneration, energy homeostasis, autophagy, and amino acid uptake. In addition, Rheb–mTORC1 signaling plays a crucial role in preventing the neurodegeneration of hippocampal neurons in the adult brain. Increasing evidence suggests that the constitutive activation of Rheb has beneficial effects against neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Our recent studies revealed that adeno-associated virus serotype 1 (AAV1) transduction with Rheb(S16H), a constitutively active form of Rheb, exhibits neuroprotective properties through the induction of various neurotrophic factors, promoting neurotrophic interactions between neurons and astrocytes in the hippocampus of the adult brain. This review provides compelling evidence for the therapeutic potential of AAV1–Rheb(S16H) transduction in the hippocampus of the adult brain by exploring its neuroprotective effects and mechanisms. View Full-Text
Keywords: Rheb(S16H); neurotrophic interaction; neurotrophic factor; Alzheimer’s disease Rheb(S16H); neurotrophic interaction; neurotrophic factor; Alzheimer’s disease
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Moon, G.J.; Shin, M.; Kim, S.R. Upregulation of Neuronal Rheb(S16H) for Hippocampal Protection in the Adult Brain. Int. J. Mol. Sci. 2020, 21, 2023.

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