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Early mitochondrial dysfunction assay for neurodegenerative diseases

36 months
Approved budget:
Professor Michael Berridge
Professor Bart Ellenbroek
Dr Melanie-Jane McConnell
Dr David Eccles
Health issue:
Neurological (CNS)
Proposal type:
Explorer Grant
Lay summary
We will develop a novel early detection assay for neurodegenerative diseases. The assay will have the potential to measure loss of mitochondrial gene expression decades before symptoms of dementure appear, at a time when sense of smell begins to decline. The concept is cross-disciplinary and is based on the unexpected finding that mitochondrial gene expression declines while expression of nuclear genes encoding respiratory complex proteins and mitochondrial ribosomal proteins remain unchanged in tumour cells lacking mitochondrial DNA and in a rat genetic model of major depressive disorder. Because compromised olfactory function is closely linked with loss of mitochondrial respiration, we see a unique opportunity to use the assay to investigate early loss of mitochondrial gene expression in models of Parkinson's disease and in the future, to test the assay in humans where neurodegenerative disease-specific molecular probes could be included in the assay.