Dysfunctional Proteolysis of Tau Protein in Alzheimer’s Disease Leads to Cell Toxicity

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease currently affecting approximately 7 million Americans. It accounts for most dementia cases and is an ultimately fatal disease. Currently, there are two FDA approved drugs that slow the progression of AD by targeting amyloid-beta plaques, but there is no known cure. Through research, two biological pathways for AD have been identified, the accumulation of amyloid-beta plaques and tau protein neurofibrillary tangles. Since evidence has shown a correlation between the onset of clinical dementia symptoms and tau pathology, it is necessary to further research its mechanism and evaluate tau protein as a potential therapeutic target for AD. This research studies dysfunctional proteolysis of tau protein as an underlying mechanism of tau pathology by determining the correlation between tau-derived peptides and neurotoxicity. Specifically, cytotoxicity assays were performed on neuroblastoma cells to evaluate each peptide’s ability to induce cell death. Identifying cytotoxic tau-derived peptides and determining their mechanism for inducing cell death can potentially identify new therapeutic strategies for AD.