Multifunctional Selenium Quantum Dots for the Treatment of Alzheimer’s Disease by Reducing Aβ-Neurotoxicity and Oxidative Stress and Alleviate Neuroinflammation

Abstract

At present, the complex pathogenesis, the difficult-to-overcome blood–brain barrier (BBB), the development of the disease course which cannot be prevented, and other problems are serious challenges in the treatment of Alzheimer’s disease (AD). In order to enhance the therapeutic effect of drugs through BBB, we synthesized simple and easy-to-obtain selenium quantum dots (SeQDs), with a multitarget therapeutic effect. This new type of SeQDs has an ultrasmall size and can quickly penetrate the BBB. According to the fluorescence characteristics of SeQDs, we can diagnose and track AD. The experimental results show that SeQDs have strong free-radical scavenging activity, protect cells from oxidative stress induced by different stimuli, and show broad-spectrum antioxidant activity. The SeQDs can not only effectively inhibit Aβ aggregation and significantly reduce Aβ-mediated cytotoxicity, thus preventing AD cascade reaction, but also effectively reduce tau protein phosphorylation by down-regulating PHF1 and CP13 and further reduce oxidative stress, restore mitochondrial functions, and maintain nerve cell stability and protect nerve cells from oxidative stress. In vivo studies demonstrate that SeQDs can continuously accumulate in the brain after rapid passage of BBB and can quickly alleviate AD, significantly improve the memory impairment of AD mice, and improve their learning and memory ability. Therefore, the use of SeQDs in the treatment of AD has great advantages compared with traditional single-target drugs and provides a new direction for the combination of prevention and treatment of neurodegenerative diseases.

The Mechanisms Underlying the Protective Action of Selenium Nanoparticles against Ischemia/Reoxygenation Are Mediated by the Activation of the Ca2+ Signaling System of Astrocytes and Reactive Astrogliosis

“…In recent decades, the role of nanoparticles in neurological diseases has been actively studied, since neurons are especially vulnerable to damage caused by oxidative stress due to high oxygen consumption, the presence of a large amount of polyunsaturated fatty acids, and a low level of expression of antioxidant enzymes [ 37 , 38 ]. The other types of brain-resident cells such as microglia and vascular endothelial cells are also targets for the treatment of neurodegeneration with selenium nanoparticles and selenium quantum dots [ 39 , 40 ].…”

Alzheimer’s Disease Association with Metals and Metalloids Concentration in Blood and Urine

“…Reduced concentration of selenium as an antioxidant could be associated with AD because of oxidative stress induced by other metals/metalloids (chromium, arsenic, etc.). Experimental studies show a decisive role of selenium in AD pathogenesis via abilities to reduce mitochondrial oxidative stress [ 60 ], to inhibit metal-induced Aβ aggregation [ 33 ] and to reduce Tau hyperphosphorylation [ 61 , 62 ]. Meanwhile, the findings of epidemiological studies are inconsistent.…”

A Transcriptomic Analysis of T98G Human Glioblastoma Cells after Exposure to Cadmium-Selenium Quantum Dots Mainly Reveals Alterations in Neuroinflammation Processes and Hypothalamus Regulation

“…The reduced expression of the pro-inflammatory cytokines induced by CdSe-QDs falls in line with the findings of Tosic and co-workers [30], who noted that graphene-QDs suppress experimental autoimmune encephalomyelitis in rats by reducing spinal cord demyelination and axonal damage, and T-helper 1 development and spinal cord inflammation, and by blocking (in vitro) T-cell-induced oligodendrocyte/neuron damage. A recent study reports that Se-QDs are able to alleviate neuroinflammation and to improve memory impairment, learning and memory ability in a mouse model of Alzheimer's disease [31]. Overall, more studies are needed to determine whether the reported alterations to immune and inflammatory pathways and processes are able to induce the adverse typically described effects or, conversely, can offer the potential beneficial effects described by Tosic et al [30] and by Guo et al [31].…”

“…A recent study reports that Se-QDs are able to alleviate neuroinflammation and to improve memory impairment, learning and memory ability in a mouse model of Alzheimer's disease [31]. Overall, more studies are needed to determine whether the reported alterations to immune and inflammatory pathways and processes are able to induce the adverse typically described effects or, conversely, can offer the potential beneficial effects described by Tosic et al [30] and by Guo et al [31].…”