Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Alpha synuclein in neurodegenerative disorders: Murderer or accomplice?

Nature Medicine volume 4, pages 755–757 (1998)Cite this article

Several neurodegenerative disorders are characterized by intracellular protein accumulations or inclusions, such as the Lewy bodies of Parkinson's disease. Although little is know about the origin of these accumulations and their specific affect on neurons, it seems likely that as they grow they prove fatal to the cell. Here Michael Brownstein and colleagues speculate on a broad role for alpha synuclein in the development of Lewy bodies and the other protein inclusions associated with neurodegeneration.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Polymeropoulos, M.H. et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045–7 (1997).

    Article  CAS  Google Scholar 

  2. Kruger, R. et al. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nature Cenet. 18, 1(1998).

    Article  Google Scholar 

  3. Spillantini, M.C. et al. Alpha-synuclein in Lewy bodies. Nature 388, 839–40 (1998).

    Article  Google Scholar 

  4. Lowe, J. et al. Ubiquitin carboxyl-terminal hydrolase (PGP9.5) is selectively present in ubiquitinated inclusion bodies characteristic of human neurodegenerative disorders. J. Pathol. 161, 153–601 (1990).

    Article  CAS  Google Scholar 

  5. li, K., Ito, H., Tanaka, K. & Hirano, A. Immunocytochemical co-localization of the proteasome in ubiquitinated structures in neurodegenerative diseases and the elderly. J. Neuropathol. Exp. Neurol. 56, 125–131 (1997).

    Article  Google Scholar 

  6. Hochstrasser, M. Ubiquitin-dependent protein degradation. Annu. Rev. Cenet. 30, 405–39 (1996).

    Article  CAS  Google Scholar 

  7. Hilt, W. & Wolf, D.H. Proteasomes: destruction as a programme. Trends Biochem. Sci. 21, 96–102 (1996).

    Article  CAS  Google Scholar 

  8. Coux, O., Tanaka, K. & Goldberg A.L. Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem. 65, 801–47 (1996).

    Article  CAS  Google Scholar 

  9. Jenco, J.M., Rawlingson, A., Daniels, B. & Morris, A.J. Regulation of phospholipase D2: selective inhibition of mammalian phospholipase D isoenzymes by alpha- and beta-synucleins. Biochem. 37, 4901–9 (1998).

    Article  CAS  Google Scholar 

  10. Maroteaux, L. & Scheller, R.H. The rat brain synucleins; family of proteins transiently associated with neuronal membrane. Mol. Brain Res. 11, 335–343 (1991).

    Article  CAS  Google Scholar 

  11. Graham, J.G. & Oppenheimer, D.R. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J. Neurol. Neurosurg. Psychiatry 32, 28–34 (1969).

    Article  CAS  Google Scholar 

  12. Quinn, N. & Wenning, G. Multiple system atrophy. Current Opinion Neurol. 8, 323–326 (1995).

    Article  CAS  Google Scholar 

  13. Papp, M.I., Kahn, J.E. & Lantos, P.L. Glial cytoplasrnic inclusions in the CMS of patients with multiple system atrophy (striatonigral degeneration, olivoponto-cerebellar atrophy, and Shy-Drager syndrome). J. Neurol. Sci. 94, 79–100 (1989).

    Article  CAS  Google Scholar 

  14. Nakazato, Y. et al. Oligodendroglial microtubular tangles in olivopontocere-bellar atrophy. J. Neuropathol. Exp. Neurol. 49, 521–530 (1990).

    Article  CAS  Google Scholar 

  15. Rosen, D.R. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59–62 (1993).

    Article  CAS  Google Scholar 

  16. Mezey, E. et al. Alpha synuclein is present in Lewy bodies in sporadic Parkinson's disease. Mol. Psychiatry (in press).

  17. DiFiglia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990–3 (1997).

    Article  CAS  Google Scholar 

  18. Paulson, H.L. et al. Ubiquitinated nuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). Neurol. 50, Suppl. 2, A310–A311 (1998).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. NINDS, NIH, 9000 Rockville Pike, Building 36, Room 3D06, Bethesda, Maryland, 20892, USA

    E. Mezey & G. Harta

  2. NHGRI, NIH, 9000 Rockville Pike, Building 49, Room 4A66, Bethesda, Maryland, 20892, USA

    A. Dehejia & M.H. Polymeropoulos

  3. Department of Neurology, Semmelweis University Medical School, IX. 6 Balassa Utca, 1083, Budapest, Hungary

    M.I. Papp

  4. NIMH/NHGRI, NIH, 9000 Rockville Pike, Building 36, Room 3D06, Bethesda, Maryland, 20892, USA

    M.J. Brownstein

Authors
  1. E. Mezey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Dehejia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Harta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M.I. Papp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M.H. Polymeropoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M.J. Brownstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mezey, E., Dehejia, A., Harta, G. et al. Alpha synuclein in neurodegenerative disorders: Murderer or accomplice?. Nat Med 4, 755–757 (1998). https://doi.org/10.1038/nm0798-755

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0798-755

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing