Schizandrin reduces cytoplasmic TDP-43 accumulation in hippocampal neuronal cells

Abstract

Transactive response DNA binding protein 43 kDa (TDP-43, encoded by the TARDBP gene) is involved in transcriptional regulation and alternative splicing process. TDP-43 proteins are located in the nucleus and shuttles transcripts to the cytoplasm in normal neurons; however, they are observed in the forms of cytoplasmic inclusions in the degenerating cells. The abnormal accumulation of TDP-43 proteins is a pathologic feature of neurodegenerative diseases, such as Lou Gehrig’s disease and dementia including frontotemporal lobar degeneration and Alzheimer’s disease. In this study, we examined whether schizandrin, a main effective compound of Schisandra chinensis (Turcz.), so called omija in Korean, reduces TDP-43 accumulation in the hippocampal neurons in vitro. An immortalized mouse hippocampal neuronal cell line, HT22 cells, were treated with a proteasome inhibitor, MG132, in the absence or presence of schizandrin. We found that schizandrin treatment increased HT22 cell viability and reduced MG132-induced cytoplasmic accumulation of TDP-43. Our results suggest that schizandrin may be a promising compound for development of functional food materials beneficial to the neuronal protection against TDP-43 proteinopathies.