New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish Creutzfeldt-Jakob kindred

Goldfarb, Lev G.; Haltia, M; Brown, Paul; Nieto, Ana Belén; Kovanen, J.; McCombie, W. Richard; Trapp, Sascha; Gajdusek, D. Carleton

doi:10.1016/0140-6736(91)91198-4

Cited by 152 publications

(52 citation statements)

References 8 publications

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“…D178N coupled with V129 produces fCJD, in which patients present with dementia and widespread deposition of PrP Sc (Goldfarb et al 1991c). If the disease mutation is coupled with M129, however, FFI results and patients present with a progressive sleep disorder that is ultimately fatal.…”

Section: Human Prion Diseasesmentioning

confidence: 99%

Prions

Colby¹,

Prusiner²

2011

Cold Spring Harbor Perspectives in Biology

458

390

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Section: Human Prion Diseasesmentioning

confidence: 99%

Prions

Colby¹,

Prusiner²

2011

Cold Spring Harbor Perspectives in Biology

458

390

View full text Add to dashboard Cite

“…73 Subsequently, a large family case series was reported by Medori et al, 74 who described an untreatable insomnia, dysautonomia, and myoclonus. Histopathologically, selective degeneration of the anteroventral Figure 4 Typical histological features of inherited prion disease 4-OPRI (96 bp), D178N and P102L.…”

Section: D178n (C532g4a)mentioning

confidence: 99%

Prion disease genetics

2006

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Prion diseases have stimulated intense scientific scrutiny since it was proposed that the infectious agent was devoid of nucleic acid. Despite this finding, genetics has played a key role in understanding the pathobiology and clinical aspects of prion disease through the effects of a series of polymorphisms and mutations in the prion protein gene (PRNP). The advent of variant Creutzfeldt-Jakob disease has confirmed one of the most powerful human genetic susceptibility factors, as all tested patients have an identical genotype at polymorphic codon 129 of PRNP. This review will also consider the accrued reports of inherited prion disease and attempt a genotype-phenotype correlation. The prospects for detection of novel genetic susceptibility factors using mouse models and human genetic association studies will be explored.

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“…Interestingly, PrPc does not seem to be an essential protein because mice with disrupted PrP genes are apparently normal at >11 mo of age (Biieler et al, 1992). Because individuals at risk for the inherited prion diseases can now be identified decades in advance of the onset of illness (Goldgaber et al, 1989;Hsiao et al, 1989Hsiao et al, , 1991Owen et al, 1989;Goldfarb et al, 1991;Prusiner, 1991), an effective pharmacological therapy that inhibits PrPSc synthesis might significantly delay the appearance of neurologic dysfunction.…”

Section: N-terminal Trimming Of Mature Prpscmentioning

confidence: 99%

Synthesis and trafficking of prion proteins in cultured cells.

Taraboulos

Raeber

Borchelt

et al. 1992

MBoC

256

214

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Scrapie prions are composed largely, if not entirely, of the scrapie prion protein (PrPSc) that is encoded by a chromosomal gene. Scrapie-infected mouse neuroblastoma (ScN2a) and hamster brain (ScHaB) cells synthesize PrPSc from the normal PrP isoform (PrPC) or a precursor through a posttranslational process. In pulse-chase radiolabeling experiments, we found that presence of brefeldin A (BFA) during both the pulse and the chase periods prevented the synthesis of PrPSc. Removal of BFA after the chase permitted synthesis of PrPSc to resume. BFA also blocked the export of nascent PrPC to the cell surface but did not alter the distribution of intracellular deposits of PrPSc. Under the same conditions, BFA caused the redistribution of the Golgi marker MG160 into the endoplasmic reticulum (ER). Using monensin as an inhibitor of mid-Golgi glycosylation, we determined that PrP traverses the mid-Golgi stack before acquiring protease resistance. About 1 h after the formation of PrPSc, its N-terminus was removed by a proteolytic process that was inhibited by ammonium chloride, chloroquine, and monensin, arguing that this is a lysosomal event. These results suggest that the ER is not competent for the synthesis of PrPSc and that the synthesis of PrPSc occurs during the transit of PrP between the mid-Golgi stack and lysosomes. Presumably, the endocytic pathway features in the synthesis of PrPSc.

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New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish Creutzfeldt-Jakob kindred

Cited by 152 publications

References 8 publications

Prions

Prions

Prion disease genetics

Synthesis and trafficking of prion proteins in cultured cells.

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