Prions and related neurological diseases

Pocchiari, Maurizio

doi:10.1016/0098-2997(94)90042-6

Cited by 68 publications

(37 citation statements)

References 439 publications

(362 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, residues within the N-terminal tail required for PrP-PrP interactions and efficient conversion include both the octapeptide repeat region and amino acids between residue 95-113. Interestingly, insertions and point mutations within this region (residues 95-113) are known to lead to genetic TSE diseases in humans (41) and have been shown to confer biochemical properties reminiscent of PrP-res on the mutated PrP-sen molecule (46).…”

Section: Discussionmentioning

confidence: 99%

N-terminal Truncation of Prion Protein Affects Both Formation and Conformation of Abnormal Protease-resistant Prion Protein Generatedin Vitro

Lawson

Priola

Wehrly

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Transmissible spongiform encephalopathy diseases are characterized by conversion of the normal proteasesensitive host prion protein, PrP-sen, to an abnormal protease-resistant form, PrP-res. In the current study, deletions were introduced into the flexible tail of PrPsen (23-124) to determine if this region was required for formation of PrP-res in a cell-free assay. PrP-res formation was significantly reduced by deletion of residues 34 -94 relative to full-length hamster PrP. Deletion of another nineteen amino acids to residue 113 further reduced the amount of PrP-res formed. Furthermore, the presence of additional proteinase K cleavage sites indicated that deletion to residue 113 generated a protease-resistant product with an altered conformation. Conversion of PrP deletion mutants was also affected by post-translational modifications to PrP-sen. Conversion of unglycosylated PrP-sen appeared to alter both the amount and the conformation of protease-resistant PrPres produced from N-terminally truncated PrP-sen. The N-terminal region also affected the ability of hamster PrP to block mouse PrP-res formation in scrapie-infected mouse neuroblastoma cells. Thus, regions within the flexible N-terminal tail of PrP influenced interactions required for both generating and disrupting PrPres formation.

show abstract

Section: Discussionmentioning

confidence: 99%

N-terminal Truncation of Prion Protein Affects Both Formation and Conformation of Abnormal Protease-resistant Prion Protein Generatedin Vitro

Lawson

Priola

Wehrly

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…All other reagents were from Sigma. The antibody against actin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) was from Santa Cruz Biotechnology. Rabbit polyclonal antibody P45-66 raised against a synthetic peptide encompassing mouse PrP (MoPrP) residues 45-66 has been described earlier (30).…”

Section: Methodsmentioning

confidence: 99%

“…Prion diseases or transmissible spongiform encephalopathies (TSEs) 1 are a group of neurodegenerative diseases affecting both animals and humans (1). Such disorders include scrapie in sheep, bovine spongiform encephalopathy in cattle, and Creutzfeldt-Jakob disease (CJD), Gerstmann-Strä ussler-Scheinker syndrome, and fatal familial insomnia in humans (2,3).…”

mentioning

confidence: 99%

Cleavage of the Amino Terminus of the Prion Protein by Reactive Oxygen Species

McMahon¹,

Mangé²,

Nishida³

et al. 2001

Journal of Biological Chemistry

145

149

View full text Add to dashboard Cite

“…Sporadic CJD occurs with a worldwide incidence of 1 in 1-2 million. In sporadic CJD there is no known exposure to the infectious CJD agent and the exact cause of disease is unclear (1).…”

mentioning

confidence: 99%

Abnormal Properties of Prion Protein with Insertional Mutations in Different Cell Types

Priola

Chesebro

1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

Inherited forms of the human transmissible spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) have been associated with mutations in the normal soluble, protease-sensitive form of the host prion protein (PrP-sen). Normal PrP protein contains five copies of a repeating eight-amino acid region, and PrP molecules with six or more copies of this region are associated with disease in familial CJD. It has been hypothesized that these mutations might facilitate spontaneous formation of the abnormal, aggregated protease-resistant PrP isoform, PrP-res, associated with clinical CJD and other transmissible spongiform encephalopathies (TSE). In the present experiments, hamster PrP molecules with 5 (wild-type), 7, 9, or 11 copies of this repeat region were generated and expressed in mouse fibroblast cells or mouse neuroblastoma cells. In mouse fibroblast cells, mutant hamster PrP molecules expressing 7, 9, and 11 copies of the octapeptide repeat sequence showed altered cell surface expression, but both mutant and wild-type hamster PrP-sen molecules demonstrated abnormal properties of aggregation and increased protease resistance. By contrast in mouse neuroblastoma cells, hamster PrP-sen with 5, 9, and 11 octapeptide repeats were expressed normally on the cell surface, but only PrP-sen molecules with 9 or 11 copies of the repeat motif had abnormal properties of aggregation and increased protease resistance. Overall, regardless of cell type, hamster PrP molecules with greater than 7 octapeptide repeats were more aggregated and more protease-resistant than molecules with 7 repeats or less. However, these abnormal molecules were at least 1000-fold less protease-resistant than bona fide PrP-res derived from TSE-infected brain tissue, and they showed no increased ability to form PrP-res in a cell-free system.The transmissible spongiform encephalopathies (TSE) 1 are a group of rare, neurodegenerative diseases which include scrapie in sheep, bovine spongiform encephalopathy in cattle and kuru, and Gerstmann-Strä ussler-Scheinker syndrome and Creutzfeldt-Jakob disease (CJD) in humans. In humans, TSE disease can occur in iatrogenic, sporadic, and familial forms. Iatrogenic CJD is associated with exposure to CJD contaminated materials such as dura mater, corneal transplants, or cadaver-derived human growth hormone. Sporadic CJD occurs with a worldwide incidence of 1 in 1-2 million. In sporadic CJD there is no known exposure to the infectious CJD agent and the exact cause of disease is unclear (1).Familial TSE are forms of CJD or Gerstmann-Strä usslerScheinker syndrome which vary in disease incubation times and clinical presentation and are associated with both point and insertion mutations in the PrP gene (see Pocchiari (1) for review). The insertion mutations occur in a portion of the PrP gene that has five copies of a repeating eight amino acid region and involve extra copies of this motif (2-7). In families with insertional mutations onset of disease is usually early in life and the disease course is long, sometimes lasting...

show abstract

Prions and related neurological diseases

Cited by 68 publications

References 439 publications

N-terminal Truncation of Prion Protein Affects Both Formation and Conformation of Abnormal Protease-resistant Prion Protein Generatedin Vitro

N-terminal Truncation of Prion Protein Affects Both Formation and Conformation of Abnormal Protease-resistant Prion Protein Generatedin Vitro

Cleavage of the Amino Terminus of the Prion Protein by Reactive Oxygen Species

Abnormal Properties of Prion Protein with Insertional Mutations in Different Cell Types

Contact Info

Product

Resources

About