Neuroinflammation, driven by β-amyloid peptide accumulation, plays a critical role in the pathogenesis of Alzheimer’s disease, resulting in neurodegeneration and cognitive decline. Inflammatory cytoki Show more
Neuroinflammation, driven by β-amyloid peptide accumulation, plays a critical role in the pathogenesis of Alzheimer’s disease, resulting in neurodegeneration and cognitive decline. Inflammatory cytokines, particularly tumor necrosis factor (TNF), adversely affect neuronal function and survival by counteracting the neuroprotective effects of neurotrophins. Importantly, brain-derived neurotrophic factor (BDNF) has been shown to alleviate the neurotoxic effects of pro-inflammatory cytokines. While the mechanisms through which pro-inflammatory cytokines disrupt BDNF/TrkB signaling are well understood, the specific ways in which BDNF protects neurons from inflammatory damage remain unclear. We present evidence that BDNF reduces cytotoxicity and neuritic damage in cholinergic neurons (SN56) induced by TNF and β-amyloid peptide, through the downregulation of c-Jun N-terminal kinase (JNK) activation. BDNF inhibits TNF-induced JNK activation by stimulating p38 mitogen-activated protein kinase. These findings indicate that BDNF restores neuronal functionality by modulating the signaling pathways of inflammatory cytokines, such as TNF, and highlight potential therapeutic strategies to mitigate neuroinflammation-associated neurodegeneration in Alzheimer’s disease. The online version contains supplementary material available at 10.1007/s11064-026-04740-8. Show less
CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T-cell resp Show more
CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T-cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD43 and the T-cell receptor (TCR). We found that the glycolytic activity of this enzyme was not significantly increased in response to TCR+CD43 co-stimulation, but that PKM2 was tyrosine phosphorylated, suggesting that it was performing moonlight functions. We report that phosphorylation of both Y Show less