The Transcellular Spread of Cytosolic Amyloids, Prions, and Prionoids

Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
Neuron (Impact Factor: 15.05). 12/2009; 64(6):783-90. DOI: 10.1016/j.neuron.2009.12.016
Source: PubMed


Recent reports indicate that a growing number of intracellular proteins are not only prone to pathological aggregation but can also be released and "infect" neighboring cells. Therefore, many complex diseases may obey a simple model of propagation where the penetration of seeds into hosts determines spatial spread and disease progression. We term these proteins prionoids, as they appear to infect their neighbors just like prions--but how can bulky protein aggregates be released from cells and how do they access other cells? The widespread existence of such prionoids raises unexpected issues that question our understanding of basic cell biology.

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Available from: Adriano Aguzzi
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    • "In 2008, it was proposed that misfolded -syn that has been released from neurons into the extracellular space can be taken up by adjacent cells where it seeds further aggregation of endogenous protein [13]. This process was suggested to underpin the spreading of Lewy neuropathology from one brain region to another [14] [15] [16] [17] [18] [19]. Thus, this hypothesis might explain the progressive, stereotypical spreading of intraneuronal -syn aggregates in PD in accordance with the six neuropathological stages proposed by Braak [20] [21]. "
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