Selenium-core nanozymes dynamically regulates Aβ & neuroinflammation circulation: Augmenting repair of nervous damage

The entangled dynamic circulation between beta-amyloid (A beta) and neuroinflammation is the main reason for the failure of monotherapy in Alzheimer's disease (AD) at present. Excessive reactive oxygen/nitrogen species (RONS) plays a crucial role in this cycle and is a key factor in the mutual promotion of A beta aggregation and neuroinflammation. Herein, we reported a multifunctional selenium-polydopamine nanozyme (Se@PDA@Bor) with broad-spectrum antioxidant activity, thereby blocking this vicious circulation. Se@PDA@Bor could effectively protect normal cells from oxidative damage by scavenging RONS, and restore mitochondrial homeostasis. In addition, Se@PDA@Bor could shift the balance of microglia activation from the pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype, and restore its phagocytic ability to A beta and nerve repair function. Furthermore, Se@PDA@Bor also had the potential to inhibit the accumulation of A beta, prevent the retriggering of neuroinflammation, and avoid the re-formation of the vicious circle. As a result, such nanozymes was able to modulate the neuroprotective function of microglia and astrocytes in a short time, ameliorate neuroinflammation, reduce A beta burden, and ultimately save memory decline and cognitive impairment in APP/PS1 transgenic AD mice. These results indicate that the well-designed nanozymes has significant benefits compared to the conventional single-target agents in the treatment of AD.

Automated summary

The multifunctional selenium-polydopamine nanozyme reported in this study effectively blocks the entangled dynamic circulation between Aβ and neuroinflammation through broad-spectrum antioxidant activity. This nanozyme protects cells from oxidative damage, improves neuroinflammation, reduces Aβ burden, and saves cognitive impairment.