MYGALIN: A SPIDER-DERIVED MOLECULE IN THE CONTEXT OF ALZHEIMER’S DISEASE

Mygalin is an acylpolyamine isolated from the spider Acanthoscurria gomesiana and has been reported as a potent bioactive molecule with immunomodulatory and neuroprotective properties. This interface motivated us to evaluate its potential in the context of Alzheimer’s disease (AD). Initially, its anti-amyloidogenic activity was investigated using a thioflavin T fluorescence aggregation assay, monitoring amyloid-β (Aβ) fibrillization kinetics in the presence of Mygalin (1:1; 10 μM; 30 h; 37 °C). Under these conditions, Mygalin significantly reduced aggregation compared with control. Next, cytocompatibility was assessed in two human cell lineages: microglial T0251 cells and differentiated neuroblastoma SH-SY5Y cells. Mygalin concentrations ranging from 25 to 150 μM showed no significant toxicity in T0251 cells, as evaluated by MTT and LDH assays after 24 h of exposure, while SH-SY5Y cells tolerated concentrations up to 200 μM. Notably, immunocytochemistry assays demonstrated that co-treatment with Mygalin (50 μM) significantly reduced Aβ oligomer binding (2 μM) to differentiated SH-SY5Y cells compared with controls. In parallel, microglial activation was evaluated in T0251 cells following Mygalin treatment and appeared to be induced in a concentration-dependent manner. Finally, in vivo experiments are currently underway using 11-month-old 3xTg-AD mice treated with Mygalin and subjected to behavioral tests followed by hippocampal Aβ quantification. Overall, this study highlights Mygalin as a promising natural compound in the AD context and underscores the value of bioprospecting bioactive molecules from biodiversity as a driver of translational biology before irreplaceable compounds are lost to anthropogenic pressures.