Fundamentals of Neurodegeneration and Protein Misfolding Disorders by Martin Beckerman

Author:Martin Beckerman
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

7.1 Prions Take an Invasion Route from the Gut to the Brain

Full length, normal PrP is a cell-surface glycoprotein attached to the extracytoplasmic surface of neurons and other cell types by means of a C-terminal glycosylphosphatidylinositol (GPI) anchor. One of the first questions that may be asked is how do disease-causing forms of this protein get to the brain from the stomach? This type of passage occurs following ingestion of contaminated brain tissue in the case of kuru and contaminated cattle feed in the case of bovine spongiform encephalopathy (BSE), or mad cow disease, in the recent outbreak in Great Britain. As illustrated in Fig. 7.1 several different kinds of immune cells facilitate the uptake from the intestinal lumen. That initial step is followed by entry into the lymphatic system and from there into the nervous system and on to the brain.

Fig. 7.1Schematic depictions of the possible invasion routes leading from the gut to the brain taken by prions. (a) Prion uptake in the intestinal lumen by various means including: M-cell transcytosis (i), intestinal epithelial cell transcytosis (ii), or direct capture by dendritic cells (iii). In addition, while phagocytic cells such as macrophages may degrade PrPSc (iv) dendritic cells may deliver them to follicular dendritic cells where early accumulation takes place (v). (b) Amplification in the lymphoid tissues is followed by invasion of the nervous system via peripheral nerves; (c) PrPSc retrograde transport and propagation along neuronal processes either along the cell surface (i), through extracellular deposits (ii), or by means of vesicle-mediated mechanisms (iii) (from Cobb Biochemistry 48: 2574 © 2009 American Chemical Society and reprinted with their permission)

Download

Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.