Abstract

  Neurodegenerative disease is a debilitating and incurable condition that affects millions. It results in the loss of function and eventual death of neural cells. It has been established that exposure of model neuronal-derived cell lines to the proteasome inhibitor MG132 emulates in vitro neurodegeneration as evidenced by a marked decrease in protein degradation concomitant with an increase in aggregate intracellular ubiquitinated proteins and endoplasmic reticulum (ER) stress (via upregulation of CHOP/GADD153). Consequently, apoptosis ensues corresponding to the upregulation of p53, activation of caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and DNA condensation/fragmentation. In this study, we investigated the potential neuroprotective function of niclosamide and its associated signaling mechanisms in SH-SY5Y and PC12 neural cells exposed to MG132. All markers of MG132-induced neurodegeneration, including the accumulation of ubiquitinated proteins, were prevented by exposure to niclosamide. In addition, niclosamide was shown to induce autophagy independently and to enhance autophagy induced by MG132. These results show that niclosamide may serve as a potential neuroprotective agent through its ability to inhibit proteasome dysfunction-induced protein ubiquitination.

Keywords: Neurodegeneration; Proteasome Dysfunction; Protein Ubiquitination; ER Stress; Apoptosis; Autophagy; Niclosamide; Neuroprotection

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Citation

Citation: Benxu Cheng., et al. “Evidence of a Neuroprotective Function for Niclosamide in Human SH-SY5Y Neuroblastoma and Rat PC12 Neural Cells". Acta Scientific Neurology 3.9 (2020): 85-94.

Copyright

Copyright: © 2020 Benxu Cheng., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.