Spectinabilin ameliorates Amyloid beta neurotoxicity through the CREB Signaling Pathway
This study aimed to investigate the neuroprotective effects and mechanisms of spectinabilin, a compound isolated from the marine bacterium Streptomyces spectabilis, in models of Alzheimer's disease. We hypothesized that spectinabilin would provide multi-faceted protection against AD related pathology, primarily through modulation of the cAMP response element-binding protein signaling pathway, a key regulator of genes involved in synaptic plasticity, mitochondrial function, and neuronal survival that is often impaired in early AD. To test this, we used both in vitro and in vivo approaches, including HT22 hippocampal neurons subjected to glutamate-induced excitotoxicity and C. elegans models expressing amyloid beta. Our objectives were to assess spectinabilin's ability to counteract neuronal death triggered by glutamate and amyloid beta oligomers, reduce amyloid beta aggregation, and improve functional outcomes in vivo. A key goal was to determine whether these benefits involved activation of the CREB pathway and upregulation of its downstream targets. This work identifies spectinabilin as a promising marine-derived candidate for AD therapy, acting through CREB-dependent enhancement of synaptic resilience. These findings support the further development of spectinabilin as a potential disease-modifying agent capable of targeting multiple aspects of AD pathology.