BDNF Protects Against Neuronal Damage Induced by TNF and β-Amyloid Peptides by Targeting JNK Activation.
📄 Abstract
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.