Molecular Biology Commons^™

Prion-Like C-Terminal Domain Of Tdp-43 And Α-Synuclein Interact Synergistically To Generate Neurotoxic Hybrid Fibrils, Shailendra Dhakal, Courtney E. Wyant, Hannah E. George, Sarah E. Morgan, Vijayaraghavan Rangachari

Faculty Publications

Aberrant aggregation and amyloid formation of tar DNA binding protein (TDP-43) and α-synuclein (αS) underlie frontotemporal dementia (FTD) and Parkinson’s disease (PD), respectively. Amyloid inclusions of TDP-43 and αS are also commonly co-observed in amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB) and Alzheimer disease (AD). Emerging evidence from cellular and animal models show colocalization of the TDP-43 and αS aggregates, raising the possibility of direct interactions and co-aggregation between the two proteins. In this report, we set out to answer this question by investigating the interactions between αS and prion-like pathogenic C-terminal domain of TDP-43 (TDP-43 PrLD). PrLD …