Mironov A, Latawiec D, Wille H, Bouzamondo-Bernstein E, Legname G, Williamson RA, Burton D, Dearmond SJ, Prusiner SB, Peters PJ. Cytosolic prion protein in neurons. J Neurosci. 2003 Aug 6;23(18):7183-93. PubMed.
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Lund University
Mironov et al. utilize immuno-EM to localize PrPc within neurons and their processes in brain. Especially interestingly, they describe a subpopulation of neurons with markedly elevated PrPc labeling. More speculative is their interpretation that, in these neurons, increased PrPc localizes to the “cytosol.” Given the resolution limitations of their EM, it seems difficult to exclude the possibility that this PrPc resides on or within smaller endosomal or tubulovesicular organelles.
This paper underscores the importance of immuno-EM in determining the subcellular localization of disease-linked peptides, and provides further parallels between prion diseases and AD, two neurodegenerative diseases associated with dementia, neuronal loss, and cerebral plaques. The authors indicate that the elevated PrPc levels are not associated with morphological abnormalities or markers of apoptosis, also pointing out that EM is the gold standard for determination of apoptosis.
In the AD field, our lab has demonstrated by immuno-EM that Aβ accumulates within neurons and their processes/synapses with β-amyloidosis and is associated with morphological alterations. It will be interesting for the authors to follow up their EM studies on PrP to define the ultrastructural site(s) of PrP accumulation with the onset of prion pathology. Many questions remain, and they are remarkably similar to questions now being asked in AD. For example, do the neurons with elevated PrP further accumulate PrP along with the disease process? If so, could this intracellular pool of PrP play a direct role in initiating pathology, and by what mechanism does extracellular PrP influence intracellular PrP and vice versa?
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