Protective effect of natural antioxidants on Olfactory Ensheathing Cells exposed to amyloid-?: biological and molecular studies

Alzhèimer Disease (AD), one of the most common neurodegenerative diseases, is characterized by progressive neuronal loss and accumulation of neurotoxic proteins, including Amyloid-beta (A?). It is known that tissue transglutaminase (TG2), an ubiquitary calcium-dependent protein, is involved in protein aggregation in AD. Previous our studies showed that A?(1-42) and its fragments A?(25-35) and A?(35-25) induced an overexpression of TG2 on Olfactory Ensheathing Cells (OECs), a glial population of the olfactory system that express neural stem cell markers, including Nestin. In the last years, growing attention rose on neuronutraceutics and their effect on mental health. Among these molecules, we focused our research on indicaxanthin and astaxanthin, natural compounds that are able to cross the blood-brain barrier. In this study, the effect of indicaxanthin or astaxanthin pre-treatment on TG2 expression in OECs exposed to A? was immunocytochemically evaluated by Vimentin and Glial Fibrillary Acid Protein (GFAP) expression. The percentage of cell viability by MTT test and the apoptotic pathway activation were also evaluated. Since Nestin, a marker of neural precursors, is co-expressed in pluripotent stem cells with cyclin D1, a marker of cellular proliferation, the effect of indicaxanthin and astaxanthin pre-treatment on their expression was also tested. We found that indicaxanthin or astaxanthin pre-treatment was able to reduce TG2 overexpression, decreasing GFAP and Vimentin levels. In addition, both compounds inhibited apoptotic pathway activation and induced an increase in the Nestin and cyclin D1 expression. These results show that indicaxanthin and astaxanthin are able to prevent the TG2 change conformation induced by A?. Our data demonstrate that indicaxanthin or astaxanthin pre-treatment stimulated OECs self-renewal through the reparative activity played by TG2. Therefore, indicaxanthin and astaxanthin might represent an innovative mechanism to contrast TG2 overexpression in AD