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.

  • Letter to the Editor
  • Published:

The 5′-untranslated region of Parkinson's disease α-synuclein messengerRNA contains a predicted iron responsive element

Molecular Psychiatry volume 12, pages 222–223 (2007)Cite this article

α-Synuclein is the 140 amino acid presynaptic protein1, 2 that forms Lewy bodies and other lesions in a spectrum of brain disorders referred to as synucleinopathies, which include Parkinson's disease, the second most common neurodegenerative disorder, as well as dementia with Lewy bodies, Lewy body variant of Alzheimer's disease, multiple system atrophy, and neurodegeneration with brain iron accumulation type I.3, 4 A causative role for α-synuclein in neurodegeneration is established by the presence of missense mutations and multiplication of the α-synuclein gene in rare families with autosomal dominant Parkinson's disease.3, 4, 5, 6 Thus, factors that regulate production and steady-state levels of α-synuclein are potentially relevant to pathogenesis.

Brain iron homeostasis is known to be disrupted in Parkinson's disease and other synucleinopathies such as neurodegeneration with brain iron accumulation type I,7 but the link between iron and α-synuclein pathology has remained unclear. Iron homeostasis is achieved in part by post-transcriptional regulation through highly conserved messenger RNA (mRNA) stem loops called iron regulatory elements (IREs), which are present in the untranslated regions (UTRs) of a number of transcripts essential to iron metabolism.7, 8 Here we provide the first report of a putative IRE in the 5′-UTR of mRNA encoding the 140-residue α-synuclein and predict that this RNA structure post-transcriptionally regulates α-synuclein protein production in response to cellular iron and redox events.

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

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

Figure 1

References

  1. Maroteaux L, Campanelli JT, Scheller RH . J Neurosci 1988; 8: 2804–2815.

  2. Ueda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M et al. Proc Natl Acad Sci USA 1993; 90: 11282–11286.

  3. Jellinger KA . Mov Disord 2003; 18 (Suppl 6): S2–S12.

  4. Lee VM, Trojanowski JQ . Neuron 2006; 52: 33–38.

  5. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A et al. Science 1997; 276: 2045–2047.

  6. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J et al. Science 2003; 302: 841.

  7. Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR . Nat Rev Neurosci 2004; 5: 863–873.

  8. Rogers JT, Randall JD, Cahill CM, Eder PS, Huang X, Gunshin H et al. J Biol Chem 2002; 277: 45518–45528.

  9. Zuker M . Science 1989; 244: 48–52.

  10. http://www.ncbi.nlm.nih.gov/Genbank/GenbankSearch.html.

Download references

Author information

Authors and Affiliations

  1. Neurochemistry Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

    A L Friedlich & J T Rogers

  2. Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

    A L Friedlich, R E Tanzi & J T Rogers

  3. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

    A L Friedlich & J T Rogers

  4. Department of Psychiatry, Harvard Medical School, VA Healthcare System, Brockton, MA, USA

    A L Friedlich

  5. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

    R E Tanzi

Authors
  1. A L Friedlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R E Tanzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J T Rogers
    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

Friedlich, A., Tanzi, R. & Rogers, J. The 5′-untranslated region of Parkinson's disease α-synuclein messengerRNA contains a predicted iron responsive element. Mol Psychiatry 12, 222–223 (2007). https://doi.org/10.1038/sj.mp.4001937

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001937

Search

Advanced search

Quick links