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Seminar Louise Serpell, University of Sussex

On October 12, 2021

Seminar given by Louise Serpell, University of Sussex « Pathological proteins and Alzheimer’s disease »

Seminar given by Louise Serpell, University of Sussex
« Pathological proteins and Alzheimer's disease »

Presentation :

Protein misfolding is central to many diseases including Alzheimer's disease. However, the mechanism by which conformational change is initiated remains elusive. Alzheimer's disease is characterised by key proteins including Tau, Amyloid-beta and by the risk factor isoform Apolipoprotein E4. However, the role of each of these in the neurodegenerative disease cascade is unclear. Our work aims to explore the initiation events that lead to misfolding and the downstream effects on neuronal function, whilst clarifying the potentially toxic species. In this talk, I will describe work that aims to uncover fundamental mechanisms at the heart of the structural changes in Amyloid-beta, tau and ApoE4.
Amyloid beta and Tau deposition pathological hallmarks of Alzheimer's disease while possession of ApoE4 is the major genetic risk factor for developing AD, providing a genetic background which leads to susceptibility to developing disease. Amyloid beta rapidly self-assembles and oligomeric species have been previously shown to affect neuronal health. We have studied the uptake and effects on organelles including lysosomes and synaptic vesicles to dissect mechanisms that lead to neuronal dysfunction and cell death. We reveal damage to specific organelles of the cell which are accompanied by impaired synaptic vesicle release and reuptake Tau is a natively unfolded protein which, unlike Amyloid-beta, does not readily self-assemble. We have developed a model fragment which self-assembles to form paired helical filaments in vitro which we have used to examine cellular mechanisms of transmission and toxicity.  We consider the underlying mechanisms that may consolidate these findings and explore potential therapies.

Biography :

Prof. Louise Serpell is Professor of Biochemistry and a Director of Sussex Neuroscience. She works within School of Life Sciences and her research bridges Neuroscience and Biochemistry. She is a member of the Neuroscience subject research area and a member of the Board of Study for Biochemistry. She is co-director of the Alzheimer's Society Doctoral Training Centre and co-lead for the Dementia Research Group. Prof. Serpell runs a research group that focusses on protein misfolding and self-assembly. A major focus is protein misfolding in neurodegenerative diseases, particularly Alzheimers disease. The research group use multidisciplinary approaches including structural biology, chemical biology, molecular biophysics, cell biology, neuroscience and neurobiology. The research is funded by Alzheimer's Society, Royal Society, EPSRC, BBSRC, MRC, Alzheimer's Research UK, ARC and TauRX therapeutics/Wista.
Place(s) :
Amphi Gilbert Simondon, bâtiment sud-ouest, niveau 1

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