Trans-activation response DNA-binding protein (TDP-43) accumulation is the major component of protein inclusions found in patients with amyotrophic lateral sclerosis. TDP-43 is predominantly located in the nucleus, however, in disease it mislocalizes to the cytoplasm where it aggregates to form inclusions. Knockdowns of karyopherin-beta and cellular apoptosis susceptibility protein resulted in marked cytoplasmic accumulation of TDP-43. We propose that the latter protein associated with defective nuclear transport may play a mechanistic role in the pathogenesis of the TDP-43 lobar degeneration.
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