Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers

Figure 5

Scheme showing a possible mechanism to explain ATX neuroprotection over the deleterious effects of AβOs. AβOs promote increased ROS generation and induce abnormal Ca²⁺ signals in primary hippocampal neurons, which arise initially from Ca²⁺ entry through NMDA receptors; these entry signals are subsequently amplified by Ca²⁺ release through RyR channels costimulated by Ca²⁺ and the increased ROS levels generated response to AβOs [25]. Activation of RyR-mediated Ca²⁺ release by ROS [59, 77] induces mitochondrial Ca²⁺-uptake, which is prevented by ryanodine at inhibitory concentrations [27]. These abnormal cytoplasmic Ca⁺² signals promote NFATc4 translocation, which induces deleterious changes in gene expression and dendritic spine morphology [42]. ATX and NAC, either by scavenging ROS/RNS or by increasing antioxidant defenses, would prevent abnormal AβOs induced RyR-mediated Ca²⁺-induced Ca²⁺ release and thus would prevent the harmful effects of enhanced NFAT nuclear translocation.