Promising in Vitro anti-Alzheimer Properties for a Ruthenium(III) Complex

Metal complexes represent today an attractive class of experimental anti-Alzheimer agents with the potential of blocking β-amyloid 1-42 aggregation and scavenging its toxicity. Three representative ruthenium(III) complexes, namely NAMI A, KP1019, and PMRU20, were specifically evaluated to this end in an established in vitro model of AD relying on primary cortical neurons. Notably, PMRU20 turned out to be highly effective in protecting cortical neurons against Aβ 1-42 toxicity, while the other tested ruthenium compounds were poorly active or even inactive; we also found that PMRU20 is virtually devoid of any significant toxicity in vitro at the applied concentrations. Interestingly, PMRU20 was neuroprotective even against the toxicity induced by Aβ 25-35. The direct reaction of PMRU20 with Aβ 1-42 was explored through ESI MS analysis and some adduct formation evidenced. In addition, thioflavin T assays revealed that PMRU20 greatly reduces Aβ 1-42 aggregation. The implications of these findings are discussed in relation to emerging treatment strategies for the Alzheimer's disease.