Protein kinases that phosphorylate 14-3-3 and transmissible spongiform encephalopathies

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Project objective

Research objectives and content The Y isoform of 14-3-3 has recently been found to be highly sensitive and specific ( 98%) marker in a spinal fluid test for the diagnosis of Creutzfeldt-Jacob disease, CJD in the early clinical stages. Dr Aitken's laboratory has now established that the same isoforms of 14-3-3 are present in cerebrospinal fluid (CSF) samples from humans and cows. Moreover, the isoforms of 14-3-3 present in CSF are principally gamma and Dr Aitken's colleagues have strong evidence for the existence of a phosphorylated form of Y 14-3-3 in brain. The project will therefore focus on the examination of these 14-3-3 isoforms and study of their particular variants (particularly phosphorylation) to test whether changes occur in the brain (and in which tissue). The work will include identification of site(s) of phosphorylation and the identification of the kinase(s) responsible. Training content (obJective, benefit and expected impact) The finding that 14-3-3 isoform(s) are a highly sensitive and specific marker in the spinal fluid test for the diagnosis in the clinical stages of CJD does not reveal the biological mechanism of onset or transmissibility of the disease. I wish to test changes in phosphorylation of 14-3-3 isoforms in neural tissue and the relationship to the TSE diseases. This may give some indication as to the possible mechanism of onset of the disease and perhaps suggest possible treatment.

Original text from CORDIS.

Participants

• MRC National Institute for Medical Research · LondonCoordinatorUnited Kingdom
• Not availableCity levelSpain

Links

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