Background: Increasing evidence indicates that amyloid β oligomer (AβO) is toxic to neurons in Alzheimer’s disease (AD) brain. The aim of the present study is to evaluate the effects of honokiol on AβO-induced learning and memory dysfunction in mice. Methods: AD mice model was established by AβO intrahippocampal injection. The cognitive function was evaluated using Morris water maze (MWM). Nissl staining was used to examine the hippocampal neuron damage. Primary hippocampal neurons were exposed to AβO. The apoptosis in the hippocampal tissues and primary neurons was assessed using terminal dexynucleotidyl transferase-mediated dUTP nick end labeling-neuronal nuclei (NeuN) and Hoechst staining, respectively. The mitochondrial membrane potential and radical oxygen species were detected using standard methods. Western blotting assay was used to check the expression levels of apoptotic and nuclear factor kappa-B (NF-κB) signaling-associated proteins and electrophoretic mobility shift assay was used to detect NF-κB-DNA binding. Results: Honokiol increased the time spend in the target zone of the AD mice in the MWM. In addition, honokiol dose-dependently attenuated AβO-induced hippocampal neuronal apoptosis, reactive oxygen species production and loss of mitochondrial membrane potential. Furthermore, AβO-induced NF-κB activation was inhibited by honokiol, as well as the upregulated amyloid precursor protein and β-secretase. Conclusion: Honokiol attenuates AβO-induced learning and memory dysfunction in mice and it may be a potential candidate in AD therapy.

Published studies on the associations between glutathione S-transferase (GST) polymorphisms and Alzheimer's disease reported controversial findings. A meta-analysis of published studies was performed to assess the associations between polymorphisms of GSTM1, GSTT1 and GSTP1, and Alzheimer's disease. PubMed, Embase, and other databases were searched for case-control on the associations between polymorphisms of GSTM1, GSTT1 and GSTP1, and Alzheimer's disease. The odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the associations. Eleven articles were finally included into the meta-analysis, including eight studies on GSTM1 null genotype, six studies on GSTT1 null genotype, and six studies on GSTP1 Ile105Val polymorphism. Overall, GSTM1 null genotype was associated with increased risk of Alzheimer's disease (fixed effect OR = 1.34, 95% CI 1.10-1.64, P = 0.004). GSTT1 null genotype was not associated with risk of Alzheimer's disease (random effect OR = 1.15, 95% CI 0.68-1.92, P = 0.60). Besides, GSTP1 Ile105Val polymorphism was significantly associated with increased risk of Alzheimer's disease (Val vs Ile: OR = 1.45, 95% CI 1.05-1.99, P = 0.023; ValVal vs IleIle: OR = 1.87, 95% CI 1.30-2.69, P = 0.001; ValVal vs IleIle + IleVal: OR = 1.76, 95% CI 1.24-2.51, P = 0.002). No obvious risk of publication bias was observed in the meta-analysis. GSTM1 null genotype and GSTP1 Ile105Val polymorphism are associated with increased risk of Alzheimer's disease. More studies with large sample size are needed to validate the findings in the meta-analysis.

The proneural (PN) and mesenchymal (MES) subtypes of glioblastoma multiforme (GBM) are robust and generally consistent with classification schemes. GBMs in the MES subclass are predominantly primary tumors that, compared to PN tumors, exhibit a worse prognosis; thus, understanding the mechanism of MES differentiation may be of great benefit for the treatment of GBM. Nuclear factor kappa B (NF-κB) signaling is critically important in GBM, and activation of NF-κB could induce MES transdifferentiation in GBM, which warrants additional research. NUDT21 is a newly discovered tumor-associated gene according to our current research. The exact roles of NUDT21 in cancer incidence have not been elucidated. Here, we report that NUDT21 expression was upregulated in human glioma tissues and that NUDT21 promoted glioma cell proliferation, likely through the NF-κB signaling pathway. Gene set enrichment analysis, western blotting, and quantitative real-time reverse transcription polymerase chain reaction confirmed that NF-κB inhibitor zeta (NFKBIZ) was a downstream target affected by NUDT21 and that the MES identity genes in glioblastoma cells, CHI3L1 and FN1, were also differentially regulated. Our results suggest that NUDT21 is an upstream regulator of the NF-κB pathway and a potential molecular target for the MES subtype of GBM.

Memantine non-competitively blocks the N-methyl-d-aspartate receptor in order to inhibit beta-amyloid (Aβ) secretion, and has been used to treat moderate-to-severe Alzheimer's disease (AD). However, the mechanisms underlying the role of memantine in the autophagy and apoptosis of neuronal cells in AD, as well as the association between neuronal autophagy and apoptosis have yet to be elucidated. The present study aimed to establish an AD cell model overexpressing the 695-amino-acid Swedish mutant of Aβ precursor protein (APP695swe) in order to observe the effects of memantine on the cell viability, autophagy and apoptosis of SH-SY5Y cells in the AD model, and to investigate the associated underlying mechanisms. A pcDNA3.1-APP695 plasmid was transfected into the SH-SY5Y cells. Reverse transcription-quantitative polymerase chain reaction and western blot analyses demonstrated that the AD cell model was successfully established. MTT assays demonstrated that memantine was able to upregulate neuronal cell survival, and acridine orange staining and flow cytometry demonstrated that memantine (5 µM) was able to inhibit neuronal autophagy and apoptosis. Following neuronal autophagy induction by rapamycin, cell apoptosis rates increased significantly. Further experiments revealed that memantine was able to upregulate the expression of signaling molecules phosphorylated (p)-phosphoinositide 3-kinase, p-Akt and p-mammalian target of rapamycin (mTOR), and also inhibited the phosphorylation of the B-cell lymphoma 2/Beclin-1 complex via mitogen-activated protein kinase 8. In conclusion, the results of the present study demonstrated that in the AD cell model, autophagy was able to promote apoptosis. Memantine exerted anti-autophagic and anti-apoptotic functions, and mTOR-dependent as well as-independent autophagic signaling pathways were involved in this process. Therefore, these results of the present study strongly supported the use of memantine as a potential therapeutic strategy for AD treatment.