Niclosamide affects intracellular TDP-43 distribution in motor neurons, activates mitophagy, and attenuates morphological changes under stress

Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron loss in the brain and spinal cord; however, its etiology unknown, no curative treatment exists. TAR DNA-binding protein 43 (TDP-43), encoded TARDBP, a genetic mutation observed 2–5% of familial ALS, TDP known to be mislocalized cytoplasm. This study aimed identify compounds that inhibited nuclear cytoplasmic localization TDP-43 human induced pluripotent stem (iPS) cells-derived neurons. transgenic iPS cells were constructed, differentiated into neurons, then treated with MG-132 sodium arsenite (stressors) induce TDP-43. STAT3 inhibitors, such as niclosamide, prevented mislocalization degraded aggregates, attenuated morphological changes under stress. Furthermore, niclosamide activated mitophagy via PINK1-parkin-ubiquitin pathway. These findings suggest may therapeutic candidate for ALS.