Guodong Huang

Due to its extremely complex pathogenesis, no effective drugs to prevent, delay progression, or cure Alzheimer’s disease (AD) exist at present. The main pathological features of AD are senile plaques composed of β-amyloid, neurofibrillary tangles formed by hyperphosphorylation of the tau protein, and degeneration or loss of neurons in the brain. Many risk factors associated with the onset of AD, including gene mutations, aging, traumatic brain injury, endocrine and cardiovascular diseases, education level, and obesity. Growing evidence points to chronic stress as one of the major risk factors for AD, as it can promote the onset and development of AD-related pathologies via a mechanism that is not well known. The use of murine stress models, including restraint, social isolation, noise, and unpredictable stress, has contributed to improving our understanding of the relationship between chronic stress and AD. This review summarizes the evidence derived from murine models on the pathological features associated with AD and the related molecular mechanisms induced by chronic stress. These results not only provide a retrospective interpretation for understanding the pathogenesis of AD, but also provide a window of opportunity for more effective preventive and identifying therapeutic strategies for stress-induced AD.

There is a growing evidence that Fyn kinase is upregulated in glioblastoma multiforme (GBM), where it plays a key role in tumor proliferation and invasion. In the present study, the antitumor effects of rosmarinic acid (RA), a Fyn inhibitor, were explored in human‑derived U251 and U343 glioma cell lines. These cells were treated with various concentrations of RA to determine its effects on proliferation, migration, invasion, apoptosis, and gene and protein expression levels. The CCK‑8 assay revealed that RA significantly suppressed cell viability of U251 and U343 cells. Furthermore, RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expression levels of invasion‑related factors, such as matrix metalloproteinase (MMP)‑2 and MMP‑9. TUNEL staining revealed that RA resulted in a dose‑dependent increase of U251 and U343 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl‑2 was downregulated and that of the pro‑apoptotic proteins Bax and cleaved caspase‑3 was increased. In addition, it was revealed that the phosphatidylinositol 3‑kinase (PI3K)/Akt/nuclear factor‑κB (NF‑κB) signaling pathway was involved in RA‑induced cytotoxicity in U251 and U343 cells. Collectively, the present study suggested RA as a drug candidate for the treatment of GBM.

Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumour. Patients with GBM respond poorly to chemotherapy and have poor survival outcomes. Neuron‐glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), has been shown to contribute to critical processes, such as cell survival, proliferation, and chemotherapy resistance, during glioma progression. In this study, we found that furanodienone (FUR), a diene‐type sesquiterpene isolated from the rhizomes of Rhizoma curcumae, exhibited a potential cytotoxic effect on temozolomide (TMZ)–resistant GBM cells in vitro by inhibiting CSPG4 and related signalling pathways. Studies investigating the mechanism demonstrated that FUR suppressed CSPG4‐Akt‐ERK signalling, inflammatory responses, and cytokine levels but activated caspase‐dependent pathways and mitochondrial dysfunction. Furthermore, an immunofluorescence assay and a dual‐luciferase reporter assay revealed that inhibition of EGR1‐mediated transcription might have contributed to the FUR‐dependent blockade of CSPG4 signalling and glioma cell survival. These results established a link between FUR‐induced CSPG4 inhibition and the suppression of EGR1‐dependent transcription. Attenuation of ERK1/2 and cytokine signalling might have generated the EGR1‐dependent negative feedback loop of the CSPG4 pathway during FUR‐induced apoptosis. These findings suggested that FUR could be a therapeutic candidate for the treatment of malignant glioma via targeting CSPG4 signalling.