Stress-related cytoplasmic TDP-43 aggregation and its role in neuronal apoptosis in a cell culture model of PGRN deficiency Alzheimer Disease

Dr. William Jia
University of British Columbia

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.

Imagine a world without Alzheimer disease.