Stable Knockdown of Drp1 in SH-SY5Y neuroblastoma cells improves retinoic acid-BDNF-induced neuronal differentiation through global transcriptomic changes

on retinoic acid-BDNF-induced neuronal differentiation and mitochondrial network organization during differentiation. We used lentiviral technology to generate an SH-SY5Y cell line with stably depleted Drp1 (shDrp1). Our transcriptomic analysis demonstrated that stable knockdown of Drp1 upregulates genes involved in nervous system development, including synapse assembly, neurogenesis, differentiation, and morphogenesis. Our results indicate that reducing Drp1 promotes transcriptional changes, improves retinoic acid-BDNF-induced neuronal differentiation with decreased ERK1/2 activation, and reduces the formation of toxic mHtt aggregates in vitro. We propose that downregulating Drp1 promotes cell survival and prevents neurotoxicity. Thus, Drp1 may be an attractive target to study further with respect to future strategies to combat neurodegenerative diseases.