Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Biomedical Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9434 Online ISSN: 2049-9442
Journal Cover
March-2015 Volume 3 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2015 Volume 3 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review

Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review)

  • Authors:
    • Min‑Tae Jeon
    • Sang Ryong Kim
  • View Affiliations / Copyright

    Affiliations: School of Life Sciences, Kyungpook National University, Daegu 702‑701, Republic of Korea
  • Pages: 137-140
    |
    Published online on: December 9, 2014
       https://doi.org/10.3892/br.2014.397
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Although there are ongoing intensive research efforts, no effective pharmacological therapies for Parkinson's disease (PD) have been developed thus far. However, with the development of efficient gene delivery systems, gene therapy for PD has become a focus of research and increasing evidence suggests that continuous production of neurotrophic factors play a significant role in the functional restoration of the nigrostriatal dopaminergic (DA) system. Our recent study reported that the transduction of DA neurons with ras homolog enriched in brain, which has an S16H mutation [Rheb(S16H)], protected the nigrostriatal DA projection in a neurotoxin model of PD in vivo. In addition, Rheb(S16H) expression significantly increased the levels of glial cell line‑derived neurotrophic factor and brain‑derived neurotrophic factor, which contributed to the neuroprotective effects of Rheb(S16H) in DA neurons in the adult brain, indicating that the activation of the signaling pathways involved in cell survival by a specific gene delivery, such as Rheb(S16H) to adult neurons, may be a useful strategy to protect neural systems in the adult brain. In the present study, a brief overview of our recent studies is provided, which demonstrates the neuroprotective mechanisms of Rheb(S16H) on the nigrostriatal DA projection in the adult brain.
View Figures

Figure 1

View References

1 

Burke RE and O'Malley K: Axon degeneration in Parkinson's disease. Exp Neurol. 246:72–83. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Jung UJ, Leem E and Kim SR: Naringin: a protector of the nigrostriatal dopaminergic projection. Exp Neurobiol. 23:124–129. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Leem E, Nam JH, Jeon MT, et al: Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease. J Nutr Biochem. 25:801–806. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Savitt JM, Dawson VL and Dawson TM: Diagnosis and treatment of Parkinson disease: molecules to medicine. J Clin Invest. 116:1744–1754. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Bartus RT, Weinberg MS and Samulski RJ: Parkinson's disease gene therapy: success by design meets failure by efficacy. Mol Ther. 22:487–497. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Coune PG, Schneider BL and Aebischer P: Parkinson's disease: gene therapies. Cold Spring Harb Perspect Med. 2:a0094312012. View Article : Google Scholar : PubMed/NCBI

7 

Ren X, Zhang T, Gong X, Hu G, Ding W and Wang X: AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model. Exp Neurol. 248:148–156. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Kim SR, Kareva T, Yarygina O, Kholodilov N and Burke RE: AAV transduction of dopamine neurons with constitutively active Rheb protects from neurodegeneration and mediates axon regrowth. Mol Ther. 20:275–286. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Kim SR, Chen X, Oo TF, Kareva T, Yarygina O, Wang C, During M, Kholodilov N and Burke RE: Dopaminergic pathway reconstruction by Akt/Rheb-induced axon regeneration. Ann Neurol. 70:110–120. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Allen SJ, Watson JJ, Shoemark DK, Barua NU and Patel NK: GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther. 138:155–175. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Lin LF, Doherty DH, Lile JD, Bektesh S and Collins F: GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science. 260:1130–1132. 1993. View Article : Google Scholar : PubMed/NCBI

12 

Manfredsson FP, Okun MS and Mandel RJ: Gene therapy for neurological disorders: challenges and future prospects for the use of growth factors for the treatment of Parkinson's disease. Curr Gene Ther. 9:375–388. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Siegel GJ and Chauhan NB: Neurotrophic factors in Alzheimer's and Parkinson's disease brain. Brain Res Brain Res Rev. 33:199–227. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Howells DW, Porritt MJ, Wong JY, Batchelor PE, Kalnins R, Hughes AJ and Donnan GA: Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra. Exp Neurol. 166:127–135. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Studer L, Spenger C, Seiler RW, Othberg A, Lindvall O and Odin P: Effects of brain-derived neurotrophic factor on neuronal structure of dopaminergic neurons in dissociated cultures of human fetal mesencephalon. Exp Brain Res. 108:328–336. 1996. View Article : Google Scholar : PubMed/NCBI

16 

Pochon NA, Menoud A, Tseng JL, Zurn AD and Aebischer P: Neuronal GDNF expression in the adult rat nervous system identified by in situ hybridization. Eur J Neurosci. 9:463–471. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Seroogy KB, Lundgren KH, Tran TM, Guthrie KM, Isackson PJ and Gall CM: Dopaminergic neurons in rat ventral midbrain express brain-derived neurotrophic factor and neurotrophin-3 mRNAs. J Comp Neurol. 342:321–334. 1994. View Article : Google Scholar : PubMed/NCBI

18 

Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP and Lindsay RM: BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature. 350:230–232. 1991. View Article : Google Scholar : PubMed/NCBI

19 

Chauhan NB, Siegel GJ and Lee JM: Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson's disease brain. J Chem Neuroanat. 21:277–288. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Nam JH, Leem E, Jeon MT, et al: Induction of GDNF and BDNF by hRheb(S16H) transduction of SNpc neurons: neuroprotective mechanisms of hRheb(S16H) in a model of Parkinson's disease. Mol Neurobiol. May 25–2014.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

21 

Aron L and Klein R: Repairing the parkinsonian brain with neurotrophic factors. Trends Neurosci. 34:88–100. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Kholodilov N, Kim SR, Yarygina O, Kareva T, Cho JW, Baohan A and Burke RE: Glial cell line-derived neurotrophic factor receptor-α1 expressed in striatum in trans regulates development and injury response of dopamine neurons of the substantia nigra. J Neurochem. 116:486–498. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Creedon DJ, Tansey MG, Baloh RH, Osborne PA, Lampe PA, Fahrner TJ, Heuckeroth RO, Milbrandt J and Johnson EM Jr: Neurturin shares receptors and signal transduction pathways with glial cell line-derived neurotrophic factor in sympathetic neurons. Proc Natl Acad Sci USA. 94:7018–7023. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Selvaraj S, Sun Y, Watt JA, Wang S, Lei S, Birnbaumer L and Singh BB: Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling. J Clin Invest. 122:1354–1367. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Datta SR, Brunet A and Greenberg ME: Cellular survival: a play in three Akts. Genes Dev. 13:2905–2927. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Brunet A, Datta SR and Greenberg ME: Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol. 11:297–305. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Chang N, El-Hayek YH, Gomez E and Wan Q: Phosphatase PTEN in neuronal injury and brain disorders. Trends Neurosci. 30:581–586. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Karassek S, Berghaus C, Schwarten M, et al: Ras homolog enriched in brain (Rheb) enhances apoptotic signaling. J Biol Chem. 285:33979–33991. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Yan L, Findlay GM, Jones R, Procter J, Cao Y and Lamb RF: Hyperactivation of mammalian target of rapamycin (mTOR) signaling by a gain-of-function mutant of the Rheb GTPase. J Biol Chem. 281:19793–19797. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Pascual A, Hidalgo-Figueroa M, Piruat JI, Pintado CO, Gomez-Diaz R and Lopez-Barneo J: Absolute requirement of GDNF for adult catecholaminergic neuron survival. Nat Neurosci. 11:755–761. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Porritt MJ, Batchelor PE and Howells DW: Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons. Exp Neurol. 192:226–234. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Nutt JG, Burchiel KJ, Comella CL, et al: Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology. 60:69–73. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Peterson AL and Nutt JG: Treatment of Parkinson's disease with trophic factors. Neurotherapeutics. 5:270–280. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jeon MT and Kim SR: Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review). Biomed Rep 3: 137-140, 2015.
APA
Jeon, M., & Kim, S.R. (2015). Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review). Biomedical Reports, 3, 137-140. https://doi.org/10.3892/br.2014.397
MLA
Jeon, M., Kim, S. R."Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review)". Biomedical Reports 3.2 (2015): 137-140.
Chicago
Jeon, M., Kim, S. R."Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review)". Biomedical Reports 3, no. 2 (2015): 137-140. https://doi.org/10.3892/br.2014.397
Copy and paste a formatted citation
x
Spandidos Publications style
Jeon MT and Kim SR: Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review). Biomed Rep 3: 137-140, 2015.
APA
Jeon, M., & Kim, S.R. (2015). Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review). Biomedical Reports, 3, 137-140. https://doi.org/10.3892/br.2014.397
MLA
Jeon, M., Kim, S. R."Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review)". Biomedical Reports 3.2 (2015): 137-140.
Chicago
Jeon, M., Kim, S. R."Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo (Review)". Biomedical Reports 3, no. 2 (2015): 137-140. https://doi.org/10.3892/br.2014.397
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team