Induction of GDNF and BDNF by hRheb(S16H) Transduction of SNpc Neurons: Neuroprotective Mechanisms of hRheb(S16H) in a Model of Parkinson’s Disease
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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In animal models of Parkinson's disease, BDNF enhances the survival of dopaminergic neurons.
“In animal models of Parkinson’s disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance.”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [93]
In the vast majority of studies with BDNF administration before induction of parkinsonism, the results revealed at least partial prevention of neuronal cell loss.
“In the vast majority of studies with BDNF administration before induction of parkinsonism, the research results revealed at least partial prevention of neuronal cell loss [89,90,92,93,99,101].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [93]
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Erythropoietin as a Modulator of Pathology in a Toxicant Mouse Model of Parkinson’s Disease
Thompson, A. (2019) · doi:10.22215/etd/2019-13782 · Cited by 1 · see citing works
Goulding, S. R. (2021) · doi:10.34719/fhhg1227 · Cited by 1 · see citing works
(2015) · Therapeutic Targets for Neurological Diseases · doi:10.14800/ttnd.302
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Neuroprotection induced by neurotrophic factors
Réus, G. Z., Manosso, L. M., Botelho, M. E. M., Arent, C. O., Pedro, L. C., & Quevedo, J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23763-8.00063-4
Novel therapeutics for diverse neurodegenerative disorders
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- Authors
- Nam, J. H., Leem, E., Jeon, M.-T., Jeong, K. H., Park, J.-W., Jung, U. J., Kholodilov, N., Burke, R. E., Jin, B. K., & Kim, S. R.
- Affiliations
- Kyung Hee University (KR)
- Kyungpook National University (KR)
- Columbia University (US)
- Corresponding author
- Jin, Byung Kwan
- Kim, Sang Ryong
- ORCID
- Venue
- Molecular Neurobiology
- Published
- 2014-05-25
- Volume
- 51
- Issue
- 2
- Pages
- 487-499
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2083475861
- Cited by
- 76
- References
- 34
- Citations by year
- 2025: 5 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 12 · 2019: 4 · 2018: 8 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 7
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- Parkinson's disease, glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, dopaminergic neurons, substantia nigra, neuroprotection, mTORC1 signaling, CREB, 6-hydroxydopamine, MPP+ neurotoxicity, neurotrophic factors, gene transduction
- MeSH terms
- Ras Homolog Enriched in Brain Protein, Animals, Disease Models, Animal, Humans, Neurons, Neuropeptides, Parkinson Disease, Substantia Nigra, Rats, Sprague-Dawley, Neuroprotective Agents, Brain-Derived Neurotrophic Factor, Monomeric GTP-Binding Proteins, Glial Cell Line-Derived Neurotrophic Factor, Rats
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