Journal of Clinical & Experimental Pathology
Open Access

Abstract

Prion diseases are invariably fatal neurodegenerative diseases of humans and animals. They are most widely known as a result of their transmissible nature with Creutzfeldt Jakob Disease (CJD) being transmitted from patient to patient through blood transfusion, certain surgical procedures or by use of human-derived hormone therapies and from animals to humans during the bovine spongiform encephalopathy (BSE) outbreak in the UK. The agent that causes these diseases is primary composed of a misfolded protein, the prion protein, which through further templated misfolding events can create more disease-associated forms resulting in disease transmissibility. Whilst the role of the prion protein in disease transmission and progression is firmly established, still very little consensus on the pathways that cause cell death during disease has been reached. Oxidative stress is a feature of prion disease with markers of oxidative damage appearing in the brain in parallel with the detection of mis-folded protein. Data generated by our group has shown how cellular redox homeostasis changes as prion infection progresses from acute to chronic to eventual cell death. The results suggest that prion propagation exacerbates an apoptotic pathway whereby mitochondrial dysfunction follows mislocalization of the critical anti-oxidant enzyme superoxide dismutase-2 (SOD2) to cytosolic caspases, accelerating its degradation. Increased activity of another SOD family member, SOD1, initially compensates for reduction in SOD2 but eventually cellular capacity to maintain oxidative homeostasis is overwhelmed, thus resulting in cell death.

Biography

Cathryn Haigh is a Senior Research Fellow at the University of Melbourne, Australia. She was awarded her PhD from the Bath University, UK in 2006 and has been researching in the area of Dementia and Prion Diseases for over ten years. Her research to date has culminated in publication of over 30 papers, more than 20 invited presentations and provision of expert advice for funding agency working groups and research panel discussions.

Email: chaigh@unimelb.edu.au