Novel neuroprotective strategies in Alzheimer’s disease based on magnetic nanoparticles for mechanical stimulation and antioxidant compounds delivery

Raffa’s group recently demonstrated that low mechanical forces promote MT stabilization. As neurites may become dystrophic due to microtubules (MT) destabilization in Alzheimer’s disease (AD), the hypothesis beyond this project is that force-induced MT stabilization is neuroprotective. Cell models of neurodegeneration were set up by treatment of neural cells with AD-like stressors and exposure resulted in neurotoxic effects such as delay in axonal extension and MT destabilization. Mechanical stimulation through nano-pulling (a technique based on the use of magnetic nanoparticles, MNPs) was able to prevent delays in axonal extensions, restoring axon outgrowth to physiological levels, and compensate for MT destabilization. Moreover, MNPs for potential improved bioavailability of the antioxidant molecule of the polyphenol resveratrol were generated. In fact polyphenols, natural compounds common in plants, confer protection against oxidative damage and are already being tested in AD clinical trials. MNPs were synthesized by a sonochemical strategy, functionalized with resveratrol, and characterized chemically and physically. Their antioxidant potential was tested and the experiments proved the retention of the antioxidant scavenging activity of resveratrol on the functionalized MNPs. Moreover, the synthesized MNPs were able to induce elongation in mouse primary neurons in a nano-pulling assay.