ABSTRACT

Neurodegeneration occurs in many neurological disorders such as and Alzheimer’s disease (AD). Two proteins named progranulin (PGRN) and TDP-43 have been found to be associated with Alzheimer’s disease (AD). We have established a cell culture model that recapitulates many aspects of human PGRN deficiency and leads to changes in TDP-43 as observed in AD patients. We have also developed peptides that can effectively prevent TDP-43 neuropathies and blocking the interaction between TDP-43 and caspase 3, a crucial protein for cell death. Surprisingly, the latter also protected neurons from dying caused by other neuronal insults. We will try to understand the role of TDP-43 in neurodegeneration. Particularly, we will study why blocking the interaction between caspase 3 and TDP-43 can protect neurons. This study will help us to further our understanding about the aging process of the brain as well as mechanisms of AD and other neurodegenerative diseases.