Modulation of Amyloid β-Induced Microglia Activation and Neuronal Cell Death by Curcumin and Analogues
Ersilia De Lorenzi; Davide Franceschini; Cecilia Contardi; Rita Maria Concetta Di Martino; Francesca Seghetti; Massimo Serra; Federica Bisceglia; Andrea Pagetta; Morena Zusso; Federica Belluti
Alzheimer&rsquo:s disease (AD) is a progressive neurodegenerative disorder that is not restricted to the neuronal compartment but includes important interactions with immune cells, including microglia. Protein aggregates, common pathological hallmarks of AD, bind to pattern recognition receptors on microglia and trigger an inflammatory response, which contributes to disease progression and severity. In this context, curcumin is emerging as a potential drug candidate able to affect multiple key pathways implicated in AD, including neuroinflammation. Therefore, we studied the effect of curcumin and its structurally related analogues cur6 and cur16 on amyloid-&beta: (A&beta:)-induced microglia activation and neuronal cell death, as well as their effect on the modulation of A&beta: aggregation. Primary cortical microglia and neurons were exposed to two different populations of A&beta:42 oligomers (A&beta:42Os) where the oligomeric state had been assigned by capillary electrophoresis and ultrafiltration. When stimulated with high molecular weight A&beta:42Os, microglia released proinflammatory cytokines that led to early neuronal cell death. The studied compounds exerted an anti-inflammatory effect on high molecular weight A&beta:42O-stimulated microglia and possibly inhibited microglia-mediated neuronal cell toxicity. Furthermore, the tested compounds demonstrated antioligomeric activity during the process of in vitro A&beta:42 aggregation. These findings could be investigated further and used for the optimization of multipotent candidate molecules for AD treatment
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