Human prion disease with a G114V mutation and epidemiological studies in a Chinese family: a case series

Ye, Jing; Han, Jun; Shi, Qi; Zhang, Bao-Yun; Wang, Guirong; Tian, Chan; Gao, Chen; Chen, Jianmin; Li, Cunjiang; Liu, Zheng; Li, Xian-Zhang; Zhang, Lai-Zhong; Dong, Xiaoping

doi:10.1186/1752-1947-2-331

Cited by 32 publications

(28 citation statements)

References 5 publications

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“…The durations of the disease range from 2-18 months (median: seven months), which are somewhat shorter than that of some other kinds of genetic human prion diseases. 16,17 The onset ages and clinical durations of the cases having family history are similar as that of the ones without family history. All cases lack of typical periodic sharp wave complexes (PSWC) in EEG, even though some cases only had sharp wave but without periodicity.…”

Section: Discussionmentioning

confidence: 48%

A Chinese Creutzfeldt-Jakob disease patient with E196K mutation inPRNP

Shi

Chen

Song

et al. 2011

Prion

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Section: Discussionmentioning

confidence: 48%

A Chinese Creutzfeldt-Jakob disease patient with E196K mutation inPRNP

Shi

Chen

Song

et al. 2011

Prion

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“…However, in some special conditions, such as retrotranslocation (Wang et al 2005) and the impaired import into the ER (Rane et al 2004), PrP may mislocate in cytoplasm, forming cytosolic PrP. Some point-mutated PrPs, e.g., A117V (Rodriguez et al 2005) and G114V (Ye et al 2008) in the transmembrane region may form cytosol transmembrane form (Ctm-PrP). Our previous study also illustrates that the genetic CJD-related PrP mutants, the (Xu et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Cytosolic PrP Induces Apoptosis of Cell by Disrupting Microtubule Assembly

Wang

Jing

et al. 2010

J Mol Neurosci

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Prion protein (PrP) is able to bind with tubulin and to interfere with the formation of microtubule. To investigate the influence of accumulation of cytosolic PrP in cytoplasm on microtubule, plasmid pcDNA3.1-PrP23-230 expressing human PrP23-230 was introduced into HeLa cells. Immunoprecipitation assays identified the molecular interaction between cytosolic PrP and cellular tubulin. Confocal microscopy showed the co-localization of the expressed cytosolic PrP with tubulin in cytoplasm. Immunofluorescent assays of tubulin illustrated remarkable disruption of microtubular structures in the cells accumulated with cytosolic PrP. Meanwhile, the expressed cytosolic PrP significantly reduced cell viability and induced cell apoptosis. The amounts of microtubule protein in the cells expressing cytosolic PrP were decreased. Moreover, the levels of endogenous tubulin in the brain tissues of scrapie-infected hamsters were significantly lower than that of normal one. It highlights a close linkage between disruption of microtubule framework and cell death caused by abnormal presence of cellular PrP in cytoplasm. The association of apoptosis with microtubule-disrupting activity caused by cytosolic PrP may further provide insight into the unresolved biological function of PrP in the neurons.

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“…Following our previous studies on the G114V gCJD patient (7,8), we further investigated all the transcriptional patterns of the brain sample and compared them to those of normal brain RNA pool (control). To better understand the expression level of screened genes, we ranked them with the relative difference ratio using the following strategy: after single chip normalization, each probe set was marked as present (P) or absent (A) according to the comparison to background noise.…”

Section: Global Transcriptional Profiling Of the G114v Gcjd Patientmentioning

confidence: 99%

Global transcriptional profiling of the postmortem brain of a patient with G114V genetic Creutzfeldt-Jakob disease

Tian

Chen

et al. 2013

International Journal of Molecular Medicine

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Abstract. Familial or genetic Creutzfeldt-Jakob disease (fCJD or gCJD) is an inherent human prion disease caused by mutation of the prion protein gene (PRNP). In the present study, global expression patterns of the parietal cortex from a patient with G114V gCJD were analyzed using the Affymetrix Human Genome U133+ 2.0 chip with a commercial normal human parietal cortex RNA pool as a normal control. In total, 8,774 genes showed differential expression; among them 2,769 genes were upregulated and 6,005 genes were downregulated. The reliability of the results was confirmed using real-time RT-PCR assays. The most differentially expressed genes (DEGs) were involved in transcription regulation, ion transport, transcription, cell adhesion, and signal transduction. The genes associated with gliosis were upregulated and the genes marked for neurons were downregulated, while the transcription of the PRNP gene remained unaltered. A total of 169 different pathways exhibited significant changes in the brain of G114V gCJD. The most significantly regulated pathways included Alzheimer's and Parkinson's disease, oxidative phosphorylation, regulation of actin cytoskeleton, MAPK signaling and proteasome, which have previously been linked to prion diseases. In addition, we found some pathways that have rarely been explored in regards to prion diseases that were also significantly altered in G114V gCJD, such as axon guidance, gap junction and purine metabolism. The majority of the genes in the 10 most altered pathways were downregulated. The data of the present study provide useful insights into the pathogenesis of G114V gCJD and potential biomarkers for diagnostic and therapeutic purposes. IntroductionPrion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative disorders in humans and animals, including Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathies (BSEs) in cattle, and scrapie in sheep and goats. The conversion of prion protein (PrP), coded by the PRNP gene, from its cellular isoform PrP C to its pathogenic isoform PrP Sc through a post-translational process is considered the etiology of these diseases. As a result of the conversion, the portion of β-sheets within PrP is increased (from 3 to 45%) whereas that of α-helices decreases (from 42 to 30%), therefore causing PrP to become detergent insoluble and resistant to denaturant (isoform PrP Sc ) (1). The conversion also causes a series of histopathological changes, including the depositions of PrP Sc , spongiform degenerations, neuronal loss and astrogliosis.According to the pathomechanisms, CJD can be classified into sporadic CJD (sCJD), familial or genetic CJD (fCJD or gCJD) and iatrogenic CJD (iCJD). fCJD accounts for approximately 10-15% of all CJD cases, characterized by the genetic changes of PrP (2). To date, 56 different mutations, including residue substitutions, insertions and deletions, have been reported (3). For instance, proline to leucine mutation at the 102nd position (P102L) ...

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Human prion disease with a G114V mutation and epidemiological studies in a Chinese family: a case series

Cited by 32 publications

References 5 publications

A Chinese Creutzfeldt-Jakob disease patient with E196K mutation inPRNP

A Chinese Creutzfeldt-Jakob disease patient with E196K mutation inPRNP

Cytosolic PrP Induces Apoptosis of Cell by Disrupting Microtubule Assembly

Global transcriptional profiling of the postmortem brain of a patient with G114V genetic Creutzfeldt-Jakob disease

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