BK21 plus KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Korea.
Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Korea.
Int J Mol Sci. 2020 Mar 16;21(6):2023. doi: 10.3390/ijms21062023.
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.
脑中 Ras 同源物蛋白富集（Rheb）是哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）的关键激活剂。Rheb 激活 mTORC1 与多种过程相关，如蛋白质合成、神经元生长、分化、轴突再生、能量平衡、自噬和氨基酸摄取。此外，Rheb-mTORC1 信号在防止成年大脑中海马神经元的神经退行性变中起着至关重要的作用。越来越多的证据表明，Rheb 的组成性激活对阿尔茨海默病（AD）和帕金森病（PD）等神经退行性疾病具有有益的影响。我们最近的研究表明，腺相关病毒血清型 1（AAV1）转导 Rheb（S16H），即 Rheb 的组成性激活形式，通过诱导各种神经营养因子表现出神经保护特性，促进成年大脑中海马体中神经元和星形胶质细胞之间的神经营养相互作用。本综述通过探讨 AAV1-Rheb（S16H）转导的神经保护作用及其机制，为 AAV1-Rheb（S16H）转导在成年大脑海马体中的治疗潜力提供了有力证据。
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