In addition, In vitro studies using human dopaminergic neurons derived from induced pluripotent stem cells (iPSCs) have provided critical mechanistic insights:(1) nicotine (10 μM) activates α7 nAChRs to reduce α-synuclein oligomerization and mitochondrial fission in PD patient-derived neurons, effects blocked by the selective antagonist α-bungarotoxin; (2) α6β2 nAChR activation in SH-SY5Y cells promotes neurite outgrowth via ERK/CREB phosphorylation, which increases evidence of the neuroprotection of nicotine (Bono et al., 2019; Collo et al., 2013). This evidence concerns the gene CREB1 and Parkinson disease.