Disease relevance of Gerstmann-Straussler-Scheinker Disease

• This conversion is important for PrP amyloidogenesis, which occurs to the highest degree in the genetically determined Gerstmann-Sträussler-Scheinker disease (GSS) and prion protein cerebral amyloid angiopathy (PrP-CAA), while it is less frequently seen in other prion diseases [1].
• The prion diseases, sometimes referred to as the "transmissible spongiform encephalopathies," include kuru, Creutzfeldt-Jakob disease, and Gerstmann-Sträussler-Scheinker disease of humans as well as scrapie and bovine spongiform encephalopathy of animals [2].
• Gerstmann-Sträussler-Scheinker disease (GSS) is a cerebral amyloidosis associated with mutations in the prion protein (PrP) gene (PRNP) [3].
• We developed a cell model of Gerstmann-Sträussler-Scheinker disease, a neurodegenerative condition characterized by PrPM-containing amyloid deposits and neuronal loss, by expressing the Gerstmann-Sträussler-Scheinker haplotype Q217R-129V in human neuroblastoma cells [4].
• Considerable progress has been made deciphering the role of an abnormal isoform of the prion protein (PrP) in scrapie of animals and Gerstmann-Sträussler syndrome (GSS) of humans [5].

Psychiatry related information on Gerstmann-Straussler-Scheinker Disease

• Familial dementia with PrP-positive amyloid plaques: a variant of Gerstmann-Sträussler syndrome [6].
• A beta peptide is the amyloid in congophilic angiopathy of Alzheimer's disease, and in majority of cases of Creutzfeld-Jakob disease and Gerstmann-Sträussler-Scheinker disease [7].

High impact information on Gerstmann-Straussler-Scheinker Disease

• Amyloid fibrils in Gerstmann-Sträussler-Scheinker disease (Indiana and Swedish kindreds) express only PrP peptides encoded by the mutant allele [8].
• A mutation equivalent to P102L in the human PrP gene, associated with Gerstmann-Straussler syndrome (GSS), has been introduced into the murine PrP gene by gene targeting [9].
• Amyloid protein of Gerstmann-Sträussler-Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58 [10].
• We found no alterations other than the Leu102 change, common to Gerstmann-Sträussler syndrome, in one of the prion protein alleles of the patient with congophilic kuru plaques [11].
• We studied levels of amyloid beta-protein precursor (beta PP) in CSF from four patients affected with Gerstmann-Sträussler-Scheinker disease and one asymptomatic gene-carrier from an Indiana kindred [12].

Chemical compound and disease context of Gerstmann-Straussler-Scheinker Disease

• We show here that PrP codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at PrP codon 102 may lead to the development of Gerstmann-Sträussler syndrome [13].
• Gerstmann-Sträussler-Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients [14].
• Proteins equivalent to the mature form of the wild-type mouse prion protein (residues 23-231) or with a mutation equivalent to that associated with Gerstmann-Straüssler-Scheinker disease (proline to leucine at codon 102 in human; 101 in mouse) were expressed in E. coli [15].
• OBJECTIVE: A new variant of Gerstmann-Sträussler-Scheinker disease (GSS) was reported, which had a substitution of glutamate to lysine at codon 219 (E219K) in addition to a P102L mutation on the same allele of the PrP gene [16].
• Immunolocalization of heparan sulfate proteoglycans to the prion protein amyloid plaques of Gerstmann-Straussler syndrome, Creutzfeldt-Jakob disease and scrapie [17].

Biological context of Gerstmann-Straussler-Scheinker Disease

• The clinicopathological phenotype of the Gerstmann-Sträussler-Scheinker disease (GSS) variant linked to the codon 102 mutation in the prion protein (PrP) gene (GSS P102L) shows a high heterogeneity [18].
• We found novel variants in the open reading frame of the prion protein (PrP) gene in a family with Gerstmann-Sträussler syndrome (GSS) [19].
• The codon 105 point mutation (proline to leucine) was found on a codon 129 (Valine) PrP allele in 4 patients from 3 different Japanese families with Gerstmann-Sträussler syndrome [20].

Anatomical context of Gerstmann-Straussler-Scheinker Disease

• Gerstmann-Sträussler-Scheinker disease. II. Neurofibrillary tangles and plaques with PrP-amyloid coexist in an affected family [21].
• Cerebrospinal fluid levels of amyloid beta-protein precursor are low in Gerstmann-Sträussler-Scheinker disease, Indiana kindred [12].
• This rapid and easy method selectively labels amyloid-related component of senile plaques, but not of kuru plaques found in Gerstmann-Sträussler syndrome [22].

Gene context of Gerstmann-Straussler-Scheinker Disease

• Neurofibrillary tangles of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease share antigenic determinants with those of Alzheimer disease [23].
• Reduced cortical choline acetyltransferase activity in Gerstmann-Sträussler syndrome [24].
• Gerstmann-Sträussler-Scheinker disease is a very rare inherited disorder due to a number of different mutations in the PRP gene, characterized by abundant deposits of plaque PrPres in the cerebral grey matter [25].

References