ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
In vivo AAV1 transduction with hRheb(S16H) protects hippocampal neurons by BDNF production.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Screening potential diagnostic biomarkers for PLA2R‑associated idiopathic membranous nephropathy by WGCNA analysis and LASSO algorithm.Renal failure · 2025Article
- Application of Neurotrophic Factors as a Therapeutic Approach for Neurodegenerative Diseases.Experimental neurobiology · 2025Review
- Inhibition of Granule Cell Dispersion and Seizure Development by Astrocyte Elevated Gene-1 in a Mouse Model of Temporal Lobe Epilepsy.Biomolecules · 2024Article
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- Phosphorylated S6K1 and 4E-BP1 play different roles in constitutively active Rheb-mediated retinal ganglion cell survival and axon regeneration after optic nerve injury.Neural regeneration research · 2023Article
- Control of hippocampal prothrombin kringle-2 (pKr-2) expression reduces neurotoxic symptoms in five familial Alzheimer's disease mice.British journal of pharmacology · 2022Article
- Biochemical Mechanisms Underlying Psychedelic-Induced Neuroplasticity.Biochemistry · 2022Review
- Rheb-mTOR activation rescues Aβ-induced cognitive impairment and memory function by restoring miR-146 activity in glial cells.Molecular therapy. Nucleic acids · 2021Article
- Therapeutic Potential of AAV1-Rheb(S16H) Transduction against Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- mTOR inhibition impairs extinction memory reconsolidation.Learning & memory (Cold Spring Harbor, N.Y.) · 2021Article
- Beneficial effects of AAV1-Rheb(S16H) administration in the adult hippocampus.Neural regeneration research · 2020Article
- Induction of GDNF and GFRα-1 Following AAV1-Rheb(S16H) Administration in the HippocampusExperimental neurobiology · 2020Article
- Dynamic Fas signaling network regulates neural stem cell proliferation and memory enhancement.Science advances · 2020Article
- Upregulation of Neuronal Rheb(S16H) for Hippocampal Protection in the Adult Brain.International journal of molecular sciences · 2020Review
- Neurotrophic interactions between neurons and astrocytes following AAV1-Rheb(S16H) transduction in the hippocampus in vivo.British journal of pharmacology · 2020Article
- Gene Therapy Vector Encoding Neuropeptide Y and Its Receptor Y2 for Future Treatment of Epilepsy: Preclinical Data in Rats.Frontiers in molecular neuroscience · 2020Article
- Therapeutic Potential of AAV1-Rheb(S16H) Transduction Against Alzheimer's Disease.Journal of clinical medicine · 2019Article
- Morin Prevents Granule Cell Dispersion and NeurotoxicityExperimental neurobiology · 2018Article
- Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo.Cell death & disease · 2018Article
- Protection of nigral dopaminergic neurons by AAV1 transduction with Rheb(S16H) against neurotoxic inflammation in vivo.Experimental & molecular medicine · 2018Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent evidence has shown that Ras homolog enriched in brain (Rheb) is dysregulated in Alzheimer's disease (AD) brains. However, it is still unclear whether Rheb activation contributes to the survival and protection of hippocampal neurons in the adult brain. To assess the effects of active Rheb in hippocampal neurons in vivo, we transfected neurons in the cornu ammonis 1 (CA1) region in normal adult rats with an adeno-associated virus containing the constitutively active human Rheb (hRheb(S16H)) and evaluated the effects on thrombin-induced neurotoxicity. Transduction with hRheb(S16H) significantly induced neurotrophic effects in hippocampal neurons through activation of mammalian target of rapamycin complex 1 (mTORC1) without side effects such as long-term potentiation impairment and seizures from the alteration of cytoarchitecture, and the expression of hRheb(S16H) prevented thrombin-induced neurodegeneration in vivo, an effect that was diminished by treatment with specific neutralizing antibodies against brain-derived neurotrophic factor (BDNF). In addition, our results showed that the basal mTORC1 activity might be insufficient to mediate the level of BDNF expression, but hRheb(S16H)-activated mTORC1 stimulated BDNF production in hippocampal neurons. These results suggest that viral vector transduction with hRheb(S16H) may have therapeutic value in the treatment of neurodegenerative diseases such as AD.
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