TDP-43 and tau oligomers in Alzheimer's disease, amyotrophic lateral sclerosis, and frontotemporal dementia.

TDP-43 and tau oligomers in Alzheimer's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Neurobiol Dis. 2020 Oct 13;:105130 Authors: Montalbano M, McAllen S, Cascio FL, Sengupta U, Garcia S, Bhatt N, Ellsworth A, Heidelman EA, Johnson OD, Doskocil S, Kayed R Abstract Proteinaceous aggregates are major hallmarks of several neurodegenerative diseases. Aggregates of post-translationally modified transactive response (TAR)-DNA binding protein 43 (TDP-43) in cytoplasmic inclusion bodies are characteristic features in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Recent studies have also reported TDP-43 aggregation in Alzheimer's disease (AD). TDP-43 is an RNA/DNA binding protein (RBP) mainly present in the nucleus. In addition to several RBPs, TDP-43 has also been reported in stress granules in FTD and ALS pathologies. Despite knowledge of cytoplasmic mislocalization of TDP-43, the cellular effects of TDP-43 aggregates and their cytotoxic mechanism(s) remain to be clarified. We hypothesize that TDP-43 forms oligomeric assemblies that associate with tau, another key protein involved in ALS and FTD. However, no prior studies have investigated the interactions between TDP-43 oligomers and tau. It is therefore important to thoroughly investigate the cross-seeding properties and cellular localization of both TDP-43 and tau oligomers in neurodegenerative diseases. Here, we demonstrate the effect of t...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research