Oxidative stress-induced neuronal damage has been implicated to play a dominant role in neurodegenerative disorders, such as Alzheimer’s disease (AD). Nicotine, a principal additive compound for tobacco users, is thought as a candidate to attenuate amyloid-β-mediated neurotoxicity and NMDA-induced excitotoxicity. Previous studies demonstrated that nicotine exerted this neuroprotective action on oxidative stress. However, the mechanisms underlying how nicotine contributes on oxidative injury in immortalized hippocampal HT-22 cells remain largely unknown. Therefore, in this study we investigated that the potential effects of nicotine on hydrogen peroxide (H₂O₂)-induced oxidative injury and underlying mechanisms in HT-22 cells. We found that pretreatment with nicotine at low concentrations markedly recovered the cell cycle that was arrested at the G2/M phase in the presence of H₂O₂ through reduced intracellular ROS generation. Moreover, nicotine attenuated H₂O₂-induced mitochondrial dysfunctions. Mechanistically, the application of nicotine significantly upregulated the levels of phosphorylated Erk1/2. The neuroprotective effects of nicotine, in turn, were abolished by PD0325901, a selective Erk1/2 inhibitor. Further obtained investigation showed that nicotine exerted its neuroprotective effects via specifically activating α7 nicotinic acetylcholine receptors (α7-nAChRs). A selective inhibitor of α7-nAChRs, methyllycaconitine citrate (MLA), not only completely prevented nicotine-mediated antioxidation but also abolished expression of p-Erk1/2. Taken together, our findings suggest that nicotine suppresses H₂O₂-induced HT-22 cell injury through activating the α7-nAChR/Erk1/2 signaling pathway, which indicates that nicotine may be a novel strategy for the treatment of neurodegenerative disorders.

Diagnosis and prediction of Alzheimer's disease (AD) are increasingly pressing in the early stage of the disease because the biomarker‐targeted therapies may be most effective. Diagnosis of AD largely depends on the clinical symptoms of AD. Currently, cerebrospinal fluid biomarkers and neuroimaging techniques are considered for clinical detection and diagnosis. However, these clinical diagnosis results could provide indications of the middle and/or late stages of AD rather than the early stage, and another limitation is the complexity attached to limited access, cost, and perceived invasiveness. Therefore, the prediction of AD still poses immense challenges, and the development of novel biomarkers is needed for early diagnosis and urgent intervention before the onset of obvious phenotypes of AD. Blood‐based biomarkers may enable earlier diagnose and aid detection and prognosis for AD because various substances in the blood are vulnerable to AD pathophysiology. The application of a systematic biological paradigm based on high‐throughput techniques has demonstrated accurate alterations of molecular levels during AD onset processes, such as protein levels and metabolite levels, which may facilitate the identification of AD at an early stage. Notably, proteomics and metabolomics have been used to identify candidate biomarkers in blood for AD diagnosis. This review summarizes data on potential blood‐based biomarkers identified by proteomics and metabolomics that are closest to clinical implementation and discusses the current challenges and the future work of blood‐based candidates to achieve the aim of early screening for AD. We also provide an overview of early diagnosis, drug target discovery and even promising therapeutic approaches for AD.

Two new octanorlanostane-type triterpenes, euphraticanoids A and B (1 and 2), two new trinorsesquiterpenoids, euphraticanoids C and D (3 and 4), and eight known triterpenoids (5, 6, 8–13) along with one steroid (7) were isolated from Populus euphratica resins. The structures of these new compounds, including their absolute configurations, were characterized by spectrocsopic, chemical, and computational methods. Biological evaluation revealed that compounds 4, 7–9, 12, and 13 display neuroprotective activities in H₂O₂-induced HT-22 cells with 4, 8, and 9 occurring in a concentration-dependent manner and 7, 12, and 13 reaching the maximum effects at 20 μM. Meanwhile, the neuroprotective properties of all isolates were accessed using glutamate-induced SH-SY5Y cells and disclosed that compounds 3, 4, 8, and 9 could dose-dependently protect neural cell injury in a concentration range of 10–40 μM. Finally, a brief structure–activity relationship was briefly discussed.

Glutamate-induced neuroexcitotoxicity could be related to the pathophysiology of some neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease. Extracellular ATP exerts a wide variety of functions, such as attenuating Aβ-mediated toxicity, inhibitingN-Methyl-D-Aspartate (NMDA) receptor subunit combinations, and aggravating ischemic brain injury. However, the effect of extracellular ATP on glutamate-induced neuroexcitotoxicity remains largely unknown. Herein, we showed that extracellular ATP prevented the glutamate-induced excitotoxicityviabinding to its P2Y1 receptors. We found that excessive glutamate triggered cellular reactive oxygen species (ROS) overproduction and mitochondrial membrane potential damage, which were significantly attenuated by extracellular ATP. Besides, glutamate activated autophagy, as illustrated by the increased protein level of autophagic marker LC3II and decreased level of p62, and glutamate-induced neuroexcitotoxicity could be completely abolished by autophagy inhibitor chloroquine. In addition, we revealed that extracellular ATP activated Erk1/2 signaling to suppress autophagy and to exert its neuroprotective effects, which was further reduced by autophagy agonist rapamycin and the selective Erk1/2 inhibitor PD0325901. Taken together, our findings suggest that extracellular ATP binding to P2Y1 receptors protected against glutamate-induced excitotoxicityviaErk1/2-mediated autophagy inhibition, implying the potential of ATP for the treatment of neurodegenerative disorders.

Esophageal squamous cell carcinoma (ESCC) has a high incidence and low survival rate, necessitating the identification of novel specific biomarkers. Centromere-associated proteins (CENPs) have been reported to be biomarkers for many cancers, but their roles in ESCC have seldom been investigated. Here, the potential clinical roles of CENPs in ESCC patients were demonstrated by a systematic bioinformatics analysis. Most CENP-encoding genes were differentially expressed between tumor and normal tissues. CENPA, CENPE, CENPF, CENPI, CENPM, CENPN, CENPQ, and CENPR were upregulated universally in the three datasets. Survival analysis demonstrated that high expression of CENPE and CENPQ was positively correlated with the outcomes of ESCC patients. The CENPE-based forecast model was more accurate than the tumor-node-metastasis (TNM) staging-based model, which was classified as stage I/II vs. III/IV. More importantly, the forecast model based on the commonly upregulated CENPs exhibited a much higher area under the curve (AUC) value (0.855) than the currently known TTL, ZNF750, AC016205.1, and BOLA3 biomarkers. The nomogram model integrating the CENPs, TNM stage, and sex was highly accurate in the prognosis of ESCC patients ( ). Besides, gene set enrichment analysis (GSEA) demonstrated that CENPE expression is significantly correlated with cell cycle, G2/M checkpoint, mitotic spindle, p53, etc. Finally, in validation experiments, we also found that CENPE and CENPQ were significantly overexpressed in esophageal cancer cells. Taken together, these results clearly suggest that CENPs are clinically promising diagnostic and prognostic biomarkers for ESCC patients.

Glutamate-induced neuroexcitotoxicity causes neuronal death in neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Extracellular ATP exerts a wide variety of functions, such as attenuating Aβ-mediated toxicity, inhibiting NMDA receptor subunit combinations, and aggravating ischemic brain injury. However, the effect of extracellular ATP on glutamate-induced neuroexcitotoxicity remains largely unknown. Herein, we showed that extracellular ATP prevented the glutamate-induced excitotoxicity via binding to its P2Y1 receptors. We found that excessive glutamate triggered cellular ROS overproduction and mitochondrial membrane potential damage, which were significantly attenuated by extracellular ATP. Besides, glutamate activated autophagy, as illustrated by the increased protein level of autophagic marker LC3II and decreased level of p62, and glutamate-induced neuroexcitotoxicity could be completely abolished by autophagy inhibitor chloroquine. In addition, we revealed that extracellular ATP activated Erk1/2 signaling to suppress autophagy and to exert its neuroprotective effects, which was further reduced by autophagy agonist rapamycin and the selective Erk1/2 inhibitor PD0325901. Taken together, our findings suggest that extracellular ATP binding to P2Y1 receptors protected against glutamate-induced excitotoxicity via Erk1/2-mediated autophagy inhibition, implying the promising potential of ATP for the treatment of neurodegenerative disorders.