Sporadic and familial CJD: classification and characterisation

Gambetti, Pierluigi; Kong, Qingzhong; Zou, Wen-Quan; Parchi, Piero; Chen, Shu G.

doi:10.1093/bmb/66.1.213

Cited by 488 publications

(641 citation statements)

References 96 publications

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“…Linkages between familial prion diseases and mutations in the gene encoding human prion protein were reported and over 20 such mutations have been shown to date to segregate familial CJD, GSS and FFI [1,19,20]. The D178N mutation is one of the most intriguing disease-related mutations and leads to different phenotypes of human prion disease depending upon the polymorphism at position 129.…”

Section: Influence Of the Pathogenic Mutations On The Conformational mentioning

confidence: 99%

Instability of familial spongiform encephalopathy-related prion mutants

Watanabe

Hiraoka

Shimoyama

et al. 2008

Biochemical and Biophysical Research Communications

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We examined the influence of D177N (D178N in humans) mutation on the conformational stability of the S2 region of moPrP C with varying pHs by using the SDSL-ESR technique. The ESR spectrum of D177N at pH 7.5 was narrower than that of Y161R1, referred to as WT*. The ESR spectrum of D177N did not change when pH in the solution decreased to pH 4.0. Our results suggested that the disappearance of a salt bridge (D177-R163) induced the increase in the instability of S2 region. Moreover, the line shape of the ESR spectrum obtained from H176S neighboring the salt bridge linked to the S2 region was similar to D177N. These results indicate that the protonation of H176 is strongly associated with the stability of S2 region. These findings are important for understanding the mechanism by which the disruption of the salt bridge in the S2 region forms the pathogenic PrP Sc structure in hereditary prion disease.

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Section: Influence Of the Pathogenic Mutations On The Conformational mentioning

confidence: 99%

Instability of familial spongiform encephalopathy-related prion mutants

Watanabe

Hiraoka

Shimoyama

et al. 2008

Biochemical and Biophysical Research Communications

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“…Although sCJD is rare, with an incidence of 0.6-1.2 per million, it accounts for about 85% of all recognized human cases of prion disease (Brandel et al, 2000;Hill et al, 2003). Two predominant PrP sc types have been identified, based on the gel mobility of the PrP sc fragments resistant to proteinase K (PK) treatment, and they are associated with different CJD phenotypes (Cali et al, 2006;Gambetti et al, 2003;Monari et al, 1994;Petersen et al, 1994). Parallel to this, PRNP polymorphism at codon 129 (Met 129 →Val) modulates sensitivity to CJD, and methionine homozygosis is a risk factor for sporadic and variant CJD (Collinge, 1999;Ladogana et al, 2005;Palmer et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Involvement of Dab1 in APP processing and β-amyloid deposition in sporadic Creutzfeldt–Jakob patients

Gavı́n¹,

Ferrer²,

Rı́o³

2010

Neurobiology of Disease

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Alzheimer's disease and prion pathologies (e.g., Creutzfeldt-Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of Amyloid Precursor Protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in seventeen cases of sporadic CJD (sCJD) post mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrP sc types 1 and 2. One group, with PrP sc type 1 showed increased Dab1 phosphorylation, and lower CTF production with an absence of A deposition. The second sCJD group, which carried PrP sc type 2, showed lower levels of Dab1 phosphorylation and CTF production, and A deposition. Thus, the present observations suggest a correlation between Dab1-phosphorylation, A deposition and PrP sc type in sCJD.

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“…Western blot of brain tissues obtained at biopsy and autopsy demonstrated the presence of rPrP Sc type 1 (Figure 2), whereas neuropathological examination revealed severe spongiform degeneration, astrogliosis, and the presence of ballooned neurons associated with weak PrP immunostaining, displaying a fine granular pattern (Figures 1 and 2). 33 Cumulatively, these characteristics unquestionably define this case as sCJDVV1. 33 Our study indicated that most of the PrP in the uterus, placenta, and amniotic fluid is truncated at the N-terminal and shares gel mobility (ϳ18 kDa) with C1, a C-terminal PrP fragment generated during normal metabolism of PrP C in the brain.…”

Section: Discussionmentioning

confidence: 98%

“…33 Cumulatively, these characteristics unquestionably define this case as sCJDVV1. 33 Our study indicated that most of the PrP in the uterus, placenta, and amniotic fluid is truncated at the N-terminal and shares gel mobility (ϳ18 kDa) with C1, a C-terminal PrP fragment generated during normal metabolism of PrP C in the brain. 12 It is noteworthy that the gel mobility of the PrP fragment present in these tissues is similar to that of the urine PrP, but different from that of CSF and brain, in agreement with earlier observations.…”

Section: Discussionmentioning

confidence: 98%

Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt-Jakob Disease

Xiao

Miravalle

Yuan

et al. 2009

The American Journal of Pathology

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The vertical transmission of a prion disease from infected mothers to their offspring is believed to be one of the routes for the natural spread of animal prion diseases. Supporting this notion is the observation that prion infectivity occurs in the placenta of infected ewes. Furthermore, the prion protein (PrP), both in its cellular form (PrP C ) and its pathological isoform (PrP Sc ), has been observed at the fetal-maternal interface of scrapie-infected sheep. However, whether these features of prion infectivity also hold true for human prion diseases is currently unknown. To begin to address such an important question, we examined PrP in the uterus as well as gestational tissues, including the placenta and amniotic fluid, in a pregnant woman with sporadic Creutzfeldt-Jakob disease (CJD). Although the proteinase K (PK)-resistant prion protein, PrP27-30, was present in the brain tissues of the mother, the PrP detected in the uterus, placenta, and amniotic fluid was sensitive to PK digestion. Unlike PrP C in the brain and adjacent cerebrospinal fluid, the predominant PrP species in the reproductive and gestational tissues were N-terminally truncated, similar to urine PrP. Our study did not detect abnormal PrP in the reproductive and gestational tissues in this case of CJD. Nevertheless, examination by a highly sensitive bioassay is ongoing to ascertain possible prion infectivity from CJD in the amniotic fluid.

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Sporadic and familial CJD: classification and characterisation

Cited by 488 publications

References 96 publications

Instability of familial spongiform encephalopathy-related prion mutants

Instability of familial spongiform encephalopathy-related prion mutants

Involvement of Dab1 in APP processing and β-amyloid deposition in sporadic Creutzfeldt–Jakob patients

Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt-Jakob Disease

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