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The University of Southampton
Institute for Life Sciences

Research project: An integrated approach to CNS inflammation: cooperation between antibodies and CD8 T cells

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This project takes a multidisciplinary approach to investigate how antibody-mediated responses regulate T cell responses in the brain. Our model is not only relevant for understanding the pathogenesis of ‘Multiple Sclerosis, but also for an increasing number of neurological diseases where CD8 T cells and/or auto-antibodies have been implicated, including paraneoplastic disorders, Rasmussen encephalitis and even age-related diseases such as Alzheimer’s disease and Parkinson’s disease.

Alzheimer's disease (AD) is the most common cause of cognitive decline in the elderly. It is characterised neuropathologically by amyloid-beta (A) peptide containing plaques and phospho-tau containing tangles. There is also evidence of loss of cytoskeletal integrity. This occurs as a result of loss of tau’s microtubule-stabilising function, caused by excessive disease-related hyper-phosphorylation. In trying to establish the relationship between plaques and tangles, many studies show that A-mediated learning and memory impairments require tau. One aim of this project is to investigate whether phospho-tau mediated cytoskeletal destabilisation underpins the cross talk between tau and A in a rodent model of AD. Another aim is to identify the mechanism of action of NAP, a peptide that counteracts phospho-tau’s microtubule defects and rescues phospho-tau phenotypes in a Drosophila model of AD. The outcomes of this project will enhance our understanding of the pathogenesis of AD and identify novel disease-modifying therapeutic targets.

Funding: The Gerald Kerkut Charitable Trust.

Funding dates: 2015-2018

Related research groups

Biomedical Sciences
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