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Cell-to-cell transmission of non-prion protein aggregates

Nature Reviews Neurology volume 6, pages 702–706 (2010)Cite this article

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A Correction to this article was published on 10 January 2011

Abstract

Neurodegenerative disorders such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and Creutzfeldt–Jakob disease (CJD) are characterized by progressive accumulation of protein aggregates in selected brain regions. Protein misfolding and templated assembly into aggregates might result from an imbalance between protein synthesis, aggregation and clearance. Although protein misfolding and aggregation occur in most neurodegenerative disorders, the concept of spreading and infectivity of aggregates in the CNS has, until now, been confined to prion diseases such as CJD and bovine spongiform encephalopathy. Emerging evidence, however, suggests that prion-like spreading, involving secreted proteins such as amyloid-β and cytosolic proteins such as tau, huntingtin and α-synuclein, can occur in other neurodegenerative disorders. The underlying molecular mechanisms and the therapeutic implications of the new data are discussed in this article.

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Figure 1: Aggregate clearing, seed formation and aggregate burden.
Figure 2: Models of cell-to-cell transmission of misfolded and aggregated proteins.

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Acknowledgements

We thank Changyoun Kim for assistance with illustrations. This work was supported by NIH grants AG18440, AG022074, AG11385 and AG10435, by the Disease Network Research Program (20090084180) from the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, Republic of Korea, and by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (20090083737). S.-J. Lee is supported by the mid-career research program (2010-0015188) through an NRF grant funded by the Ministry of Education, Science and Technology.

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Authors and Affiliations

  1. Department of Biomedical Science and Technology, Konkuk University, 1 Hwayangdong, Gwangjin-gu, 143-701, Seoul, Korea

    Seung-Jae Lee

  2. Departments of Neurosciences and Pathology, University of California, San Diego, 9500 Gilman Drive, MC 0624, La Jolla, 92093, CA, USA

    Paula Desplats, Christina Sigurdson, Igor Tsigelny & Eliezer Masliah

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Contributions

S.-J. Lee, C. Sigurdson, I. Tsigelny and E. Masliah researched the data for the article. All authors contributed substantially to discussions of the content. S.-J. Lee, P. Desplats and E. Masliah contributed equally to writing the article and to review and/or editing of the manuscript before submission.

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Correspondence to Eliezer Masliah.

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Lee, SJ., Desplats, P., Sigurdson, C. et al. Cell-to-cell transmission of non-prion protein aggregates. Nat Rev Neurol 6, 702–706 (2010). https://doi.org/10.1038/nrneurol.2010.145

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