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Cellular prion protein electron microscopy: attempts/limits and clues to a synaptic trait. Implications in neurodegeneration process

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Abstract

Prion diseases are caused by an infectious agent constituted by a rogue protein called prion (PrPSc) of neuronal origin (PrPc) and are exemplified by Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. Considerable efforts have been made to understand the cerebral damage caused by these diseases but a clear comprehensive view cannot be achieved without defining the neurophysiological function of PrPc. This lack of information is in part attributable to our ignorance of the precise localization of PrPc in the brain neuronal cell. One relevant option to explore this aspect is to undertake PrP immunohistochemistry at the electron-microscopy level, knowing that this challenge raises major technical constraints. In describing the attempts and restrictions of the various approaches used, we review here the efforts that have been invested in this particular field of prionology. The common result emerging from these contributions is that the synapse could be the site at which PrPc exerts its critical activity. This location suggests, in the perspective of synaptic regulation, that PrPc can be assigned multiple biological functions and supports the novel concept that prion-like changes are involved in long-term memory formation. The synaptic trait of PrPc and PrPSc suggests that synapse loss is the key event in neuronal death. Interestingly, synaptic alterations are also considered to be predominant in the pathophysiological mechanism in Alzheimer, Parkinson and Huntington diseases. All these brain disorders, characterized by the formation of a specific amyloid protein of synaptic origin, can be classified under the heading of amyloidogenic synaptopathies.

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Acknowledgements

I wish to thank S. Braithwaithe, M.M. Ruchoux, and S. Simoneau for editing the manuscript and A. Roig for the design work.

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    Jean-Guy Fournier

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Fournier, JG. Cellular prion protein electron microscopy: attempts/limits and clues to a synaptic trait. Implications in neurodegeneration process. Cell Tissue Res 332, 1–11 (2008). https://doi.org/10.1007/s00441-007-0565-5

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