Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases

Abstract

A common feature of many neurodegenerative diseases is the deposition of β-sheet-rich amyloid aggregates formed by proteins specific to these diseases. These protein aggregates are thought to cause neuronal dysfunction, directly or indirectly. Recent studies have strongly implicated cell-to-cell transmission of misfolded proteins as a common mechanism for the onset and progression of various neurodegenerative disorders. Emerging evidence also suggests the presence of conformationally diverse 'strains' of each type of disease protein, which may be another shared feature of amyloid aggregates, accounting for the tremendous heterogeneity within each type of neurodegenerative disease. Although there are many more questions to be answered, these studies have opened up new avenues for therapeutic interventions in neurodegenerative disorders.

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Figure 1: Potential mechanisms mediating cell-to-cell transmission of cytosolic protein aggregates.
Figure 2: Hypothetical model accounting for the stereotypical progression of pathologies in Alzheimer's and Parkinson's diseases.
Figure 3: Pathological strains underlying the divergence and convergence of neurodegenerative proteinopathies.

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Acknowledgements

The authors thank J.Q. Trojanowski for critical reading of the manuscript. This study was supported by NIH/NIA grants AG17586, NS53488 (V.M.Y.L.), the Marian S. Ware Alzheimer Program, the Jeff and Anne Keefer Fund and the Parkinson Council.

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Correspondence to Virginia M Y Lee.

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Guo, J., Lee, V. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med 20, 130–138 (2014). https://doi.org/10.1038/nm.3457

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