Protective effect of astaxanthin on Olfactory Ensheathing Cells exposed to amyloid-?: biological and molecular investigation

Alzheimer's disease (AD) is characterized by agglomerated proteins constitued by amyloid-beta (A?). A? possesses neutoxic effect and is also a substrate of tissue transglutaminase (TG2), an ubiquitarian protein that plays a key role in AD. Several reports indicated that in AD is involved oxidative stress and that the treatment with antioxidants mitigates the effects of oxidative stress in the central nervous system. In particular, astaxanthin, an antioxidant with antiflammatory properties, could have an important therapeutic role in AD. Herein, we have evaluated the effect of astaxanthin pretreatment on olfactory ensheathing cells (OECs) exposed to the native peptide of A?(1-42) or its fragments A?(25-35) and A?(35-25). OECs are glial cells located in the olfactory system, the first to show a deficit in neurodegenerative diseases. Vimentin, GFAP, nestin, cyclin D1, TG2 expression and the activation of the apoptotic pathway were assessed through immunocytochemical techniques. The percentage of cell viability and ROS levels were detected. In addition, to monitor the mitochondrial status, we used delayed luminescence (DL). We found that astaxanthin was able to reduce TG2 expression up-regulated by A?, reducing also GFAP and Vimentin levels. Astaxanthin pre-treatment stimulates cellular repair increasing cyclin D1 and nestin levels and inhibing apoptotic pathway activation. In parallel, we observed a significant change of DL intensity in OECs exposed to the toxic fragment A? (25-35), that completely disappear when OECs were pre-incubated with astaxantin. Therefore, we can suggest that astaxanthin pretreatment could represent an innovative mechanism to counteract the aberrant TG2 overexpression in AD.