ArticleMolecular neurobiology2015
Induction of GDNF and BDNF by hRheb(S16H) transduction of SNpc neurons: neuroprotective mechanisms of hRheb(S16H) in a model of Parkinson's disease.
Article in Molecular neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
- Application of Neurotrophic Factors as a Therapeutic Approach for Neurodegenerative Diseases.Experimental neurobiology · 2025Review
- Intracerebellar upregulation of Rheb(S16H) ameliorates motor dysfunction in mice with SCA2.Acta pharmacologica Sinica · 2025Article
- The Role of Brain-Derived Neurotrophic Factor as an Essential Mediator in Neuronal Functions and the Therapeutic Potential of Its Mimetics for Neuroprotection in Neurologic and Psychiatric Disorders.Molecules (Basel, Switzerland) · 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
- Expression of the primate-specific LINC00473 RNA in mouse neurons promotes excitability and CREB-regulated transcription.The Journal of biological chemistry · 2023Article
- Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases.Frontiers in molecular neuroscience · 2023Review
- The Polyunsaturated Fatty Acid EPA, but Not DHA, Enhances Neurotrophic Factor Expression through Epigenetic Mechanisms and Protects against Parkinsonian Neuronal Cell Death.International journal of molecular sciences · 2022Article
- Dioscin-Mediated Autophagy Alleviates MPPMolecules (Basel, Switzerland) · 2022Article
- The neuroprotective effects of glucagon-like peptide 1 in Alzheimer's and Parkinson's disease: An in-depth review.Frontiers in neuroscience · 2022Review
- Serum BDNF discriminates Parkinson's disease patients with depression from without depression and reflect motor severity and gender differences.Journal of neurology · 2021Article
- Therapeutic Potential of AAV1-Rheb(S16H) Transduction against Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- Glial cells in Parkinson´s disease: protective or deleterious?Cellular and molecular life sciences : CMLS · 2020Review
- Therapeutic Potential of Repeated Intravenous Transplantation of Human Adipose-Derived Stem Cells in Subchronic MPTP-Induced Parkinson's Disease Mouse Model.International journal of molecular sciences · 2020Article
- Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- Beneficial effects of AAV1-Rheb(S16H) administration in the adult hippocampus.Neural regeneration research · 2020Article
- Control of Reactive Oxygen Species for the Prevention of Parkinson's Disease: The Possible Application of Flavonoids.Antioxidants (Basel, Switzerland) · 2020Review
- Induction of GDNF and GFRα-1 Following AAV1-Rheb(S16H) Administration in the HippocampusExperimental neurobiology · 2020Article
- Effect of treadmill exercise on catalepsy and the expression of the BDNF gene in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -induced Parkinson in maleIranian journal of basic medical sciences · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transduction of dopaminergic (DA) neurons with human ras homolog enriched in brain, which has a S16H mutation [hRheb(S16H)] protects the nigrostriatal DA projection in the 6-hydroxydopamine (6-OHDA)-treated animal model of Parkinson's disease (PD). However, it is still unclear whether the expression of active hRheb induces the production of neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), which are involved in neuroprotection, in mature neurons. Here, we show that transduction of nigral DA neurons with hRheb(S16H) significantly increases the levels of phospho-cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB), GDNF, and BDNF in neurons, which are attenuated by rapamycin, a specific inhibitor of mammalian target of rapamycin complex 1 (mTORC1). Moreover, treatment with specific neutralizing antibodies for GDNF and BDNF reduced the protective effects of hRheb(S16H) against 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity. These results show that activation of hRheb/mTORC1 signaling pathway could impart to DA neurons the important ability to continuously produce GDNF and BDNF as therapeutic agents against PD.
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