Abstract

Prion diseases share common features of neurodegenerative disorders, infectious diseases and pathologies linked to misfolded proteins. Whether these aspects are independently and fortuitously present in prion diseases or are somewhat linked together remains unsettled, but the contribution of genomic, proteomic, metabolomic and spectroscopic techniques might give insights into this puzzle, and likely give hope for therapy to patients. Although the prion protein gene (PRNP) governs most of the clinical and pathological features of prion diseases and plays a pivotal role in determining host susceptibility, there are still many uncertainties and unknown risk factors that need to be clarified and identified. Several genes, other than PRNP, have recently been found to be associated with a risk of developing sporadic or variant Creutzfeldt-Jakob disease, but these novel data have been produced in a relatively small number of patients and controls and, therefore, need further confirmation. The same criticism applies to the identification of the over 20 new cerebrospinal fluid or plasma markers of disease. Some of these markers seem related to the massive brain damage that occurs, rather than being specific to prion infection. Nevertheless, genomic and post-genomic approaches have shown that these techniques are very powerful, and the best way to overcome the scantiness of samples would be to encourage strong collaboration between different centers of excellence in prion diseases. In this review, we describe the most recent and outstanding advances offered by genomics and post-genomics analyses in the field of human prion diseases.

Highlights

  • Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of fatal neurological disorders that affect humans and animals, and for which there is no available therapy [1]

  • 10 to 20% of Creutzfeldt-Jakob disease (CJD) cases appear within families [4,5] and these forms are always linked to point or insert mutations in the prion protein gene, PRNP, suggesting that these disorders are strongly linked to PRNP and that, unlike

  • Sporadic and variant CJD and most of the related prion disorders are relatively easy to diagnose based upon clinical signs and available instrumental and laboratory tools, which include electroencephalography, brain-imaging techniques and detection of the marker 14-3-3 in the cerebrospinal fluid (CSF), alone or in combination with other neuron-specific, brain-derived proteins

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Summary

Introduction

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of fatal neurological disorders that affect humans and animals, and for which there is no available therapy [1]. Data are not always comparable, due to the small number of prion patients and to the choice of controls, often taken from healthy individuals without including patients with different neurodegenerative disorders, rather than being due to the techniques used These critical aspects were taken into serious consideration by Brechlin and co-workers [46], who applied stringent criteria and appropriate neurological controls for the identification of five possible markers for sporadic CJD using two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry. Not altered in the brain of sCJD Increased in AD, but at a lower level than Produced by LDH action on pyruvate - Continued overleaf

Conclusions
11. Baron T
15. Pocchiari M
18. Eaton L
27. Outram GW
Findings
30. Alpers MP
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