ObjectiveTo explore whether acrolein can induce ferroptosis in vitro and in vivo. MethodsHT22 cells were treated with acrolein and then incubated with ferroptosis inhibitor ferrostatin-1 （Fer-1） and deferoxamine （DFO）. MTT assay was used to detect the cell survival rate. Dihydroethidium （DHE） and FerroOrange probes were used to detect the contents of free radicals and ferrous ions in cells. A transmission electron microscope observed the structure of mitochondria in standard and acrolein groups. Western blot was used to detect the levels of ferroptosis-related proteins GPX4， COX-2， and FTH1 in vitro. In vivo， male C57BL/6 mice were given 3 mg/kg acrolein every day at the age of 7-8 weeks for 1， 2， and 4 weeks， and the levels of ferroptosis-related proteins GPX4， COX-2， and FTH1 in the hippocampus was detected by western blot. ResultsAcrolein significantly reduced the survival rate of HT22 cells and induced mitochondrial shrinkage， and decreased the number of cristae. Meanwhile， acrolein could remarkably increase intracellular free radical and ferrous ions. In addition， acrolein promoted the increase in the expression of Cyclooxygenase-2 （COX-2） and Ferritin Heavy Chain 1 （FTH1） at the cellular level and decreased the expression of Glutathione peroxidase 4 （GPX4）. At the animal level， acrolein promoted the increase of COX-2 expression and decreased the expressions of GPX4 and FTH1. ConclusionAcrolein induced neuronal ferroptosis in vitro and in vivo， suggesting ferroptosis inhibitors could attenuate acrolein-associated diseases in CNS， such as Alzheimer's disease.

ObjectiveTo observe whether PT109 ［5-（1，2-dithiolan-3-yl）-N-（4-（isoquinolin-5-ylamino）cyclohexyl）pentanamide］ could improve the cognitive dysfunction in sporadic AD mice induced by lateral ventricular injection of streptozotocin and study the underlying mechanisms. MethodsThirty-two seven-week-old male C57BL/6 mice were randomly divided into 4 groups： control group （7 mice）， model group （7 mice）， PT109 low dosage group （9 mice） and PT109 high dosage group （9 mice）. To establish the sporadic Alzheimer’s disease， these mice were injected with intracerebroventricular streptozotocin on the first and third day （3 mg/kg， 5 μL per injection site）. Then PT109 （30， 100 mg·kg^-1·d^-1） was injected intraperitoneally. Two weeks later， Morris water maze and step through test were used to evaluate the effect of PT109 on the learning and memory ability of AD mice. The AD related indexes such as microglia， neurons， dendritic spines and phosphorylated Tau protein were detected by immunofluorescence， immunohistochemistry， western blotting and Golgi staining. ResultsThe behavioral experiments results showed that PT109 could improve the learning and memory impairment. The immunofluorescence and immunohistochemistry staining results showed that compared with model group， PT109 reduced the number of Iba1 positive cell in hippocampus region （low dosage： P <0.001， high dosage： P <0.001） and high dosage PT109 increased the total number of MAP2 and Tuj1 positive cell in hippocampus and cortex region （P <0.05， P <0.01）. The Golgi staining results showed that compared with model group， PT109 increased the density of dendritic spines （low dosage： P <0.001， high dosage： P <0.001）. The western blotting results showed that compared with model group， PT109 decreased the protein levels of NLRP3 （high dosage： P <0.05 ） and phosphorylated Tau protein （low dosage： P <0.05， high dosage： P <0.01 ）， and high dosage PT109 increased the protein levels of PSD95 （P <0.05） and phosphorylated GSK3β （P <0.05）. ConclusionPT109 could improve the learning and memory impairment of icv-STZ mice， which might be related to the regulation of GSK3β/Tau pathway.