Acta Scientific Neurology (ASNE) (ISSN: 2582-1121)

Research Article Volume 3 Issue 9

Evidence of a Neuroprotective Function for Niclosamide in Human SH-SY5Y Neuroblastoma and Rat PC12 Neural Cells

Kevin C Bermea1, Edgar A Casillas2, Liza D Morales3, Laura L Valdez1, Brenda Bin Su1, Andrew Tsin1 and Benxu Cheng1*

1Department of Molecular Science, School of Medicine, The University of Texas Rio Grande Valley, United States of America
2Department of Physical Therapy, School of Health Professions, The University of Texas Health Science Center at San Antonio, United States of America
3Department of Human Genetics and the South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, United States of America

*Corresponding Author: Benxu Cheng, Department of Molecular Science, School of Medicine, The University of Texas Rio Grande Valley, United States of America.

Received: June 24, 2020; Published: August 31, 2020

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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.




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