The activation of immune cells in the brain is believed to be one of the earliest events in prion disease development, where misfolded PrionSc protein deposits are thought to act as irritants leading to a series of events that culminate in neuronal cell dysfunction and death. The role of these events in prion disease though is still a matter of debate. To elucidate the mechanisms leading from abnormal protein deposition to neuronal injury, we have performed a detailed network analysis of genes differentially expressed in several mouse prion model

Crespo, Isaac

del Sol Mesa, Antonio

Jurkowski, Wiktor

Kitano, H.

Rump, Kirsten

BMC Systems Biology

PubMed

Abstract
          
            Background
            The activation of immune cells in the brain is believed to be one of the earliest events in prion disease development, where misfolded PrionSc protein deposits are thought to act as irritants leading to a series of events that culminate in neuronal cell dysfunction and death. The role of these events in prion disease though is still a matter of debate. To elucidate the mechanisms leading from abnormal protein deposition to neuronal injury, we have performed a detailed network analysis of genes differentially expressed in several mouse prion models.
          
          
            Results
            We found a master regulatory core of genes related to immune response controlling other genes involved in prion protein replication and accumulation, and neuronal cell death. This regulatory core determines the existence of two stable states that are consistent with the transcriptome analysis comparing prion infected versus uninfected mouse brain. An in silico perturbation analysis demonstrates that core genes are individually capable of triggering the transition and that the network remains locked once the diseased state is reached.
          
          
            Conclusions
            We hypothesize that this locking may be the cause of the sustained immune response observed in prion disease. Our analysis supports the hypothesis that sustained brain inflammation is the main pathogenic process leading to neuronal dysfunction and loss, which, in turn, leads to clinical symptoms in prion disease.
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Isaac Crespo

Kirsten Roomp

Wiktor Jurkowski

Hiroaki Kitano

Antonio del Sol

Crossref

Gene regulatory network analysis supports inflammation as a key neurodegeneration process in prion disease

peer reviewedThe activation of immune cells in the brain is believed to be one of the earliest events in prion disease development, where misfolded PrionSc protein deposits are thought to act as irritants leading to a series of events that culminate in neuronal cell dysfunction and death. The role of these events in prion disease though is still a matter of debate. To elucidate the mechanisms leading from abnormal protein deposition to neuronal injury, we have performed a detailed network analysis of genes differentially expressed in several mouse prion model

Open Repository and Bibliography - Luxembourg

Gene regulatory network analysis supports inflammation as a key neurodegeneration process in prion disease.

Springer - Publisher Connector

https://bmcsystbiol.biomedcentral.com/track/pdf/10.1186/1752-0509-6-132?site=bmcsystbiol.biomedcentral.com

Gene regulatory network analysis supports inflammation as a key neurodegeneration process in prion disease.

Abstract

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Open Repository and Bibliography - Luxembourg

Springer - Publisher Connector