Tetsuhiro Ueda, Toshihide Takeuchi, Nobuhiro Fujikake, Mari Suzuki, Eiko N Minakawa, Morio Ueyama, Yuzo Fujino, Nobuyuki Kimura, Seiichi Nagano, Akio Yokoseki, Osamu Onodera, Hideki Mochizuki, Toshiki Mizuno, Keiji Wada, Yoshitaka Nagai
The abnormal aggregation of TDP-43 into cytoplasmic inclusions in affected neurons is a major pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 is aberrantly accumulated in the neurons of most patients with sporadic ALS/FTD and other TDP-43 proteinopathies, how TDP-43 forms cytoplasmic aggregates remains unknown. In this study, we show that a deficiency in DCTN1, a subunit of the microtubule-associated motor protein complex dynactin, perturbs the dynamics of stress granules and drives the formation of TDP-43 cytoplasmic aggregation in cultured cells, leading to the exacerbation of TDP-43 pathology and neurodegeneration in vivo...
February 4, 2024: Acta Neuropathologica Communications