Understanding the causes of DNA damage in dementia associated with abnormal TDP-43
DNA carries genes that define any living being. The genes are essential for function of the whole organism, but they are damaged everyday due to normal cellular processes and exposition to toxic agents. Therefore, efficient DNA repair mechanisms are crucial for the proper functioning of genes and the maintenance of healthy cells. Abnormal accumulation of DNA damage actively contributes to neurodegeneration in Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD), the two most common causes of dementia. However, precise mechanism underlining this phenomenon is unknown. In both, AD and FTLD, abnormal protein called TDP-43 is present. Interestingly, recently it was discovered that TDP-43 repairs DNA. Given that DNA is damaged in dementia and TDP-43 does not work properly, defective DNA repair may be a potential cause of the disease. In this project I investigate how abnormal TDP-43 damages DNA in dementia to be able to repair this mechanism and therefore treat dementia. Because damage to DNA targets genes, I also aim to identify these genes. This information will provide better understanding of the causes of dementia and will also pave way for the establishing new therapeutic strategies for dementia.
Konopka is a postdoctoral researcher, working at Macquarie University in Sydney.