Transcriptomics

The underlying conversion mechanism of PrPC into PrPSc is poorly understood and is further complicated by the existence of several different prion strains characterized by distinct tertiary and quaternary structures as well as different clinical patterns [1]. Several hypotheses exist about the contribution of unknown molecules other than PrP to prion propagation.

To address this issue, several animal studies have investigated the host response to prion infection of different origins and strains. In this context, analyses of gene expression alterations that occur in prion-infected animals represents a powerful tool that may contribute to unraveling the molecular basis of prion diseases and therefore reveal novel potential targets for diagnosis and therapeutics.

The differential gene expression after prion infection has been extensively explored (reviewed in [2]); however, most of the studies involved animal models such as mice, sheep and cattle, all distantly related to humans.

Therefore, we performed a large-scale gene expression analysis of brains from BSE-infected cynomolgus macaques (Macaca fascicularis), which are known to be an excellent model for studying human acquired prion diseases.

The results obtained with the Affymetrix® microarray platform have shown hundreds of differentially expressed transcripts, some associated to known functions in the frontal cortex [3]. These genes belong to various pathways including oxygen homeostasis, lipid metabolism and inflammation response. Interestingly, they are known to be involved in other neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, supporting the hypothesis of a potential shared mechanism underlying the onset and the development of all neurodegenerative disorders.

 


1. Legname, G., et al., Continuum of prion protein structures enciphers a multitude of prion isolate-specified phenotypes. Proc Natl Acad Sci U S A, 2006. 103(50): p. 19105-10.

2. Benetti, F., S. Gustincich, and G. Legname, Gene expression profiling and therapeutic interventions in neurodegenerative diseases: a comprehensive study on potentiality and limits. Expert Opin Drug Discov, 2012. 7(3): p. 245-59.

3. Barbisin, M., et al., Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)-infected cynomolgus macaques. BMC Genomics, 2014. 15: p. 434.

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