Prion diseases or
transmissible spongiform encephalopathies (TSEs) are human and
animal diseases naturally or experimentally transmissible with a long incubation period and a fatal course without remission. The nature of the transmissible agent remains debated but the absence of a structure evoking a conventional microorganism led Stanley B. Prusiner to hypothesize that it could be an infectious
protein (proteinaceous infectious particle or
prion). The
prion would be the abnormal form of a normal
protein, cellular PrP (PrPc) which will change its spatial conformation and be converted into
scrapie prion protein (PrPsc) with properties of partial resistance to
proteases, aggregation and insolubility in
detergents. No inflammatory or immune response are detected in TSEs which are characterized by brain damage combining spongiosis, neuronal loss, astrocytic
gliosis, and deposits of PrPsc that may appear as
amyloid plaques. Although the link between the accumulation of PrPsc and the appearance of lesions remains debated, the presence of PrPsc is constant during TSE and necessary for a definitive diagnosis. Even if they remain
rare diseases (2 cases per million), the identification of
kuru, at the end of the 1950s, of iatrogenic cases in the course of the 1970s and of the variant of
Creutzfeldt-Jakob disease (CJD) in the mid-1990s explain the interest in these diseases but also the fears they can raise for public health. They remain an exciting research model because they belong both to the group of
neurodegenerative diseases with
protein accumulation (
sporadic CJD), to the group of
communicable diseases (iatrogenic CJD, variant of CJD) but also to the group of
genetic diseases with a transmission Mendelian dominant (genetic CJD,
Gerstmann-Straussler-Scheinker syndrome,
fatal familial insomnia).