Our results are the first to demonstrate in vivo, that the GPI-anchor signal sequence plays a fundamental role in the GPI-anchor composition, dictating the subcellular localization of a given protein and, in the case of PrPC, influencing the development of prion disease.
Prion diseases are progressive chronic neurodegenerative disorders associated with the accumulation of the scrapie prion protein PrP<sup>Sc</sup>, a misfolded conformer of the cellular prion protein PrP<sup>C</sup>.
These antibodies should allow us to address questions concerning the nature of the prion protein as well as the initiation and progression of prion diseases.
RT-QuIC has been successfully used to detect PrPSc from different prion diseases with a variety of substrates including hamster, human, sheep, bank vole, bovine and chimeric forms of prion protein.
The C-terminally truncated Y145Stop variant of prion protein (PrP23-144), which is associated with heritable PrP cerebral amyloid angiopathy in humans and also capable of triggering a transmissible prion disease in mice, serves as a useful in vitro model for investigating the molecular and structural basis of amyloid strains and cross-seeding specificities.
These findings suggest that the protein expression of MTs in the astrocytes is thus regulated differentially among human prion diseases and modified locally by such abnormal prion protein depositions as kuru plaques.
Normally folded prion protein (PrP<sup>C</sup>) and its functions in healthy brains remain underappreciated compared with the intense study of its misfolded forms ("prions," PrP<sup>Sc</sup>) during the pathobiology of prion diseases.
In most human and animal prion diseases the abnormal disease-associated prion protein (PrPSc) is deposited as non-amyloid aggregates in CNS, spleen and lymphoid organs.
Prion diseases are fatal neurodegenerative disorders related to the conformational alteration of the prion protein (PrP C) into a pathogenic and protease-resistant isoform (PrPSc).
Mutations in the protein coding region of the human PrP gene (PRNP), which have been proposed to alter the stability of the PrP protein, have been linked to a number of forms of TSE.
Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal isoform of the protease-insensitive isoform (PrPSc) of prion protein.
Prion protein (PrP) (106-126) retains the neurotoxic properties of the entire pathological PrPsc and it is generally used as a reasonable model to study the mechanisms responsible for prion diseases.
Previous genetic analyses have indicated that several amino acid residues involved in the hydrophobic core of PrP (such as V180, F198, and V210) play a critical role in the development of prion diseases.
The presence of abnormal, disease-related prion protein (PrP<sup>D</sup>) has recently been demonstrated by protein misfolding cyclic amplification (PMCA) in urine of patients affected with variant Creutzfeldt-Jakob disease (vCJD), a prion disease typically acquired from consumption of prion contaminated bovine meat.
PrP(c) is encoded by the prion protein gene, and a common polymorphism at codon 129 of this gene is a determinant of susceptibility to acquired and sporadic prion diseases but not for sporadic AD.
Amino acids that differentiate ovine and deer normal host prion protein (PrP<sup>C</sup>) and associated with structural rigidity of the loop β2-α2 (S173N, N177T) appear to confer resistance to some prion diseases.
The key molecular event in the pathogenesis of TSEs is the conversion of the cellular prion protein PrP<sup>C</sup> into a disease-associated isoform PrP<sup>Sc</sup>.
Two Creutzfeldt-Jakob disease-associated PrP mutants, PrPT188K and PrPT188R, revealed a secretory pathway to the cell membrane and PrP(Sc)-like properties, i.e. enhanced proteinase K resistance and detergent insolubility similar to other mutant PrPs associated with familial prion diseases.