Autophagy is a lysosomal-mediated catabolic process that degrades different cytoplasmic components required for cellular homeostasis and cell survival in response to stress. In addition, autophagy is considered to be protective against Alzheimer's disease because genetic deletion of autophagy results in amyloidβ peptide accumulation, which enhances neurodegeneration. [6]-Gingerol, a major phenolic compound derived from ginger, has been reported to have anti-hyperglycemic, anti-inflammatory, and anti-oxidative properties, but it is currently unknown whether [6]-Gingerol induces autophagy. In the present study, we examined whether [6]-Gingerol induced autophagy in rodent neuronal NG108-15 cells. [6]-Gingerol treatment did not affect cell viability and resulted in several characteristics of autophagy, including the appearance of autophagic vacuoles, increased levels of the autophagic marker microtubule-associated protein 1 light chain 3-II (LC3-II), and an increased number of GFP-LC3 puncta. [6]-Gingerol-induced LC3-II expression occurred in a dose-dependent manner. It was additively increased by cotreatment with [6]-Gingerol and lysosome inhibitor, implicating an enhancement of autophagic flux. Furthermore, [6]-Gingerol downregulated phosphorylated Akt (Ser473 and Thr308) and phosphorylated S6 ribosomal protein (Ser235). [6]-Gingerol is an efficacious agonist of the transient receptor potential vanilloid subfamily 1 (TRPV1), which is a nonselective cation channel, and found that the calcium-signaling pathway seems to be involved in the [6]-Gingerol-induced autophagy. In summary, [6]-Gingerol induced autophagy by inhibiting the Akt/mTOR/p70S6K pathway in NG108-15 cells. We are now investigating whether the activation of AMP-activated protein kinase is associated with [6]-gingerol -induced autophagy.