Defining the role of nuclear proteostasis in the pathogenesis of fronto-temporal dementia (FTD).
The major hallmark of Fronto-temporal dementia (FTD) is the presence of protein clumps or ‘aggregates’ in affected neurons. These are present in various parts of the cell, including the nucleus, which acts as the cellular ‘brain’. Importantly, it is becoming apparent that the nucleus is an important site from where disease is initiated. However, due to the limited availability of appropriate tools, the role of protein aggregates in the nucleus and how this relates to FTD has not been previously studied. This project, using advanced tools and cellular techniques, aims to take an innovative approach to identify how these nuclear aggregates form in affected neurons in FTD. Furthermore, it aims to identify new ways to prevent the formation of these aggregates. We have found that a specific protein prevents the clumping of proteins in the nucleus. It is also protective against several other pathological events linked to FTD. However, similarly, this protein has not been previously studied in FTD. This project will therefore investigate a new cellular pathway in FTD and novel mechanisms to prevent the formation of aggregates. This study may therefore reveal novel therapeutic targets for FTD.
Dr Parakh is a post-doctoral research fellow working at the Centre for Motor Neuron Disease (MND) Research at Macquarie University, Sydney.