Prion diseases: contribution of high‐resolution immunomorphology

Abstract

The transmisible spongiform encephalopathies or prion diseases are fatal neurological diseases that occur in animals and humans. They are characterized by the accumulation in the cerebral tissue of the abnormal form of prion protein (PrP sc ) produced by a post-translational event involving conformational change of its normal cellular counterpart (PrP c ). In this short review, we present some results on the biology of prion proteins which have benefited from morphological approaches combining the electron microscopy techniques and the immunodetection methods. We discuss data concerning in particular the physiological function of the normal cellular prion prion (PrP c ) which have allowed to open up new vistas on prion diseases, the biogenesis of amyloid plaque and the cellular site involved in the prion protein conversion process.

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

“…One obstinately unsolved issue in prionology concerns the neurophysiological function of the normal counterpart of prions. The IEM approach, particularly associated with nanogold labelling technology, might efficiently contribute to the elucidate of the function of PrP c , thus yielding powerful information for the better understanding of prion diseases (Fournier and Grigoriev 2001). In this direction, a highly promising approach, which consists of the development of a fixation technique combined with acrylate embedment, has shown its efficiency in the detection of two presynaptic proteins by doublelabelling (Mahendrasingam et al 2003).…”

Prion protein (PrPc) immunocytochemistry and expression of the green fluorescent protein reporter gene under control of the bovine PrP gene promoter in the mouse brain

“…An ultrastructural immunoperoxidase study indicated a uniform distribution of PrP c at the surface of all cerebellar cells (Lainé et al, 2001) but failed to detect any differences in subcellular patterns of PrP c expression between neurons and glial cells, as well as any PrP c at the synapses. These data contrast strikingly with a recent confirmation of synaptic localization of PrP c in the hippocampus obtained by using immunogold at the ultrastructural level (Mironov et al, 2003) and several earlier studies suggesting that the synapses could be critical sites of functional PrP c expression (Collinge et al, 1994; Fournier et al, 1995, 2000; Salès et al, 1998; Herms et al, 1999; Moya et al, 2000; Haeberlé et al, 2000; Brown, 2001) where replication and propagation of PrP d could be initiated (Kitamoto et al, 1992; Grigoriev et al, 1999; Ferrer et al, 2000; Fournier and Grigoriev, 2001). Indeed, an increasing amount of data points to central synapses as the primary victims of neurodegeneration in prion diseases (Jeffrey et al, 2000; Belichenko et al, 2000; Brown et al, 2001; Siso et al, 2002; Cunningham et al, 2003).…”

Cytotoxic Intermediates in the Fibrillation Pathway: Aβ Oligomers in Alzheimer’s Disease as a Case Study

“…Research largely has focused on verifying that disease transmission is based, surprisingly, on proteins (prions) rather than nucleic acids. Prions in their abnormal, disease-state conformation are fi brillogenic, and they accumulate in diseased brain as ordered aggregates and amyloid plaques (Fournier and Grigoriev, 2001). In disease transmission, pathogenic prions convert normal cellular prions to the abnormal conformation.…”