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

Tian,Chan; Liu,Di; Chen,Chen; Xu,Yin; Gong,Han-Shi; Chen,Cao; Shi,Qi; Zhang,Bao-Yun; Han,Jun; Dong,Xiao-Ping

doi:10.3892/ijmm.2013.1239

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

Authors:
- Chan Tian
- Di Liu
- Chen Chen
- Yin Xu
- Han-Shi Gong
- Cao Chen
- Qi Shi
- Bao-Yun Zhang
- Jun Han
- Xiao-Ping Dong
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Affiliations: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China, Network Information Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China
Published online on: January 10, 2013 https://doi.org/10.3892/ijmm.2013.1239
Pages: 676-688

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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.

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1	Prusiner SB: Prions. Proc Natl Acad Sci USA. 95:13363–13383. 1998. View Article : Google Scholar : PubMed/NCBI
2	Colby DW and Prusiner SB: Prions. Cold Spring Harb Perspect Biol. 3:a0068332011. View Article : Google Scholar : PubMed/NCBI
3	Pastore M, Chin SS, Bell KL, et al: Creutzfeldt-Jakob disease (CJD) with a mutation at codon 148 of prion protein gene: relationship with sporadic CJD. Am J Pathol. 167:1729–1738. 2005. View Article : Google Scholar : PubMed/NCBI
4	Collins S, McLean CA and Masters CL: Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. J Clin Neurosci. 8:387–397. 2001. View Article : Google Scholar
5	Hwang D, Lee IY, Yoo H, et al: A systems approach to prion disease. Mol Syst Biol. 5:2522009. View Article : Google Scholar
6	Xiang W, Windl O, Westner IM, et al: Cerebral gene expression profiles in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 58:242–257. 2005. View Article : Google Scholar : PubMed/NCBI
7	Ye J, Han J, Shi Q, et al: Human prion disease with a G114V mutation and epidemiological studies in a Chinese family: a case series. J Med Case Rep. 2:3312008. View Article : Google Scholar : PubMed/NCBI
8	Shi Q, Zhang BY, Gao C, et al: The diversities of PrP(Sc) distributions and pathologic changes in various brain regions from a Chinese patient with G114V genetic CJD. Neuropathology. 32:51–59. 2012. View Article : Google Scholar : PubMed/NCBI
9	Camon E, Magrane M, Barrell D, et al: The Gene Ontology Annotation (GOA) project: implementation of GO in SWISS-PROT, TrEMBL, and InterPro. Genome Res. 13:662–672. 2003. View Article : Google Scholar : PubMed/NCBI
10	National Center for Biotechnology Information, US National Library of Medicine; Bethesda, MD: http://www.ncbi.nlm.nih.gov/geo.
11	Mukherjee A and Soto C: Role of calcineurin in neurodegeneration produced by misfolded proteins and endoplasmic reticulum stress. Curr Opin Cell Biol. 23:223–230. 2011. View Article : Google Scholar : PubMed/NCBI
12	KEGG: Kyoto Encyclopedia of Genes and Genomes. http://www.genome.jp/kegg/.
13	Rodriguez MM, Peoc’h K, Haik S, et al: A novel mutation (G114V) in the prion protein gene in a family with inherited prion disease. Neurology. 64:1455–1457. 2005. View Article : Google Scholar : PubMed/NCBI
14	Kordek R, Liberski PP, Yanagihara R, Isaacson S and Gajdusek DC: Molecular analysis of prion protein (PrP) and glial fibrillary acidic protein (GFAP) transcripts in experimental Creutzfeldt-Jakob disease in mice. Acta Neurobiol Exp. 57:85–90. 1997.
15	Tang Y, Xiang W, Hawkins SA, Kretzschmar HA and Windl O: Transcriptional changes in the brains of cattle orally infected with the bovine spongiform encephalopathy agent precede detection of infectivity. J Virol. 83:9464–9473. 2009. View Article : Google Scholar
16	Martinez T and Pascual A: Identification of genes differentially expressed in SH-SY5Y neuroblastoma cells exposed to the prion peptide 106–126. Eur J Neurosci. 26:51–59. 2007.PubMed/NCBI
17	Xiang W, Windl O, Wunsch G, et al: Identification of differentially expressed genes in scrapie-infected mouse brains by using global gene expression technology. J Virol. 78:11051–11060. 2004. View Article : Google Scholar : PubMed/NCBI
18	Zabel C, Nguyen HP, Hin SC, Hartl D, Mao L and Klose J: Proteasome and oxidative phoshorylation changes may explain why aging is a risk factor for neurodegenerative disorders. J Proteomics. 73:2230–2238. 2010. View Article : Google Scholar : PubMed/NCBI
19	Wikipedia website: http://en.wikipedia.org/wiki/Purine_metabolism.
20	Deriziotis P and Tabrizi SJ: Prions and the proteasome. Biochim Biophys Acta. 1782:713–722. 2008. View Article : Google Scholar : PubMed/NCBI
21	Li XL, Wang GR, Jing YY, et al: Cytosolic PrP induces apoptosis of cell by disrupting microtubule assembly. J Mol Neurosci. 43:316–325. 2011. View Article : Google Scholar : PubMed/NCBI
22	Nieznanski K, Podlubnaya ZA and Nieznanska H: Prion protein inhibits microtubule assembly by inducing tubulin oligomerization. Biochem Biophys Res Commun. 349:391–399. 2006. View Article : Google Scholar : PubMed/NCBI
23	Osiecka KM, Nieznanska H, Skowronek KJ, Karolczak J, Schneider G and Nieznanski K: Prion protein region 23–32 interacts with tubulin and inhibits microtubule assembly. Proteins. 77:279–296. 2009.
24	Fabrizi C, Silei V, Menegazzi M, et al: The stimulation of inducible nitric-oxide synthase by the prion protein fragment 106–126 in human microglia is tumor necrosis factor-alpha-dependent and involves p38 mitogen-activated protein kinase. J Biol Chem. 276:25692–25696. 2001.PubMed/NCBI
25	Corsaro A, Thellung S, Villa V, et al: Prion protein fragment 106–126 induces a p38 MAP kinase-dependent apoptosis in SH-SY5Y neuroblastoma cells independently from the amyloid fibril formation. Ann NY Acad Sci. 1010:610–622. 2003.
26	Corsaro A, Thellung S, Chiovitti K, et al: Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline reverses the neurotoxic effects of the prion protein fragment 90–231. Neurotox Res. 15:138–154. 2009.PubMed/NCBI
27	Higgins GC, Beart PM, Shin YS, Chen MJ, Cheung NS and Nagley P: Oxidative stress: emerging mitochondrial and cellular themes and variations in neuronal injury. J Alzheimers Dis. 20(Suppl 2): S453–S473. 2010.PubMed/NCBI
28	Tang Y, Xiang W, Terry L, Kretzschmar HA and Windl O: Transcriptional analysis implicates endoplasmic reticulum stress in bovine spongiform encephalopathy. PLoS One. 5:e142072010. View Article : Google Scholar
29	Zerial M and McBride H: Rab proteins as membrane organizers. Nat Rev Mol Cell Biol. 2:107–117. 2001. View Article : Google Scholar : PubMed/NCBI
30	Gilch S, Bach C, Lutzny G, Vorberg I and Schatzl HM: Inhibition of cholesterol recycling impairs cellular PrP(Sc) propagation. Cell Mol Life Sci. 66:3979–3991. 2009. View Article : Google Scholar : PubMed/NCBI
31	Ermolayev V, Cathomen T, Merk J, et al: Impaired axonal transport in motor neurons correlates with clinical prion disease. PLoS Pathog. 5:e10005582009. View Article : Google Scholar : PubMed/NCBI