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The Department of Biomedicine

BBB "extra" seminar: Carol MacKintosh

A 14-3-3 regulated signalling network linking diabetes and Alzheimer's disease

Monday, December 17, 14.30 - NB! Day

Carol MacKintosh
Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Scotland, UK

Why people with diabetes have an increased risk of cognitive decline and Alzheimer’s disease is unknown. We were therefore intrigued to discover that many brain proteins undergo phosphorylation when mice are deprived of food, and are co-ordinately dephosphorylated within minutes when insulin levels in the blood are restored to normal post-prandial concentrations, irrespective of glycaemic level. The regulated brain proteins include proteins that regulate neuronal cell morphology and synaptic function, including proteins implicated in Alzheimer’s disease and in regulating the need to sleep. We have developed a powerful new way to identify and study many of these insulin-sensitive brain phosphoproteins by demonstrating that they can be captured specifically by 14-3-3 proteins during food deprivation. The talk will outline how studies of two of the regulated brain proteins reveal novel reversible chains of events linking peripheral insulin to regulation of cytoskeletal remodelling and regulation of tau phosphorylation in the brain. Dysregulations of the molecular network we have uncovered may help explain links between diabetes, Alzheimer’s disease and sleep disorders.

Chairperson: Jan Haavik, Department of Biomedicine