ProfessorAnthony Don

How ageing and genetic risk precipitate neurodegenerative diseases of ageing.

The brain is the most lipid rich organ in the body with the exception of fat tissue, attributed primarily to the abundance of myelin in our nervous system. Our research team investigates how and why the dominant genetic risk factors for Alzheimer's disease affect lipid metabolism and the control of brain myelin homeostasis. We hypothesize that the abundant myelination of the human brain, while underpinning our advanced cognitive capabilities, also sensitizes us to neurodegeneration as our myelin degenerates with ageing. Since oligodendrocytes and myelin are essential for neuronal health, the natural age-dependent myelin attrition is likely to be a major driving force behind age-dependent loss of nervous system function and neurodegeneration.

Much of our brain physiology and immune system functions are dictated by lipid metabolism and lipid-derived signalling molecules that signal through G-protein coupled receptors. Our team also investigates how lipid signalling molecules control myelination in normal development and normal ageing, and how these processes are dysregulated in neurodegenerative diseases (Alzheimer's Disease, Frontotemporal Dementia, Multiple Sclerosis). 

Our research uses highly sophisticated mass spectrometry in combination with genetic disease models, and we lead internationally in developing new mass spectrometry-based approaches for understanding brain metabolism.

Control of physiological metabolism by ceramides.

Ceramides are a family of lipids that appear to act as direct sensors of dietary fat intake, feeding back to regulate cellular metabolism through the regulation of key signalling pathways. Ceramides tend to promote insulin resistance and obesity. Our research group is the first in the world to have developed potent and specific inhibitors of specific ceramide synthase enzymes, which are the enzymes that catalyse ceramide synthesis. We are creating these inhibitors to open up the international research community's understanding of a key aspect of physiological metabolism, and with a view to creating new drugs to treat obesity and diabetes.