Amyloid-Beta Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms on Olfactory Ensheathing Cells: Modulatory Effect of Indicaxanthin

Alzhèimer Disease (AD) is characterized by protein aggregates in the brain, including amyloid-beta (Aβ), a substrate for tissue transglutaminase (TG2). We assessed the effect of full native peptide of Aβ (1–42), the fragments (25–35 and 35–25) on TG2 expression and its isoforms (Long and Short) on mouse Olfactory Ensheathing Cells (OECs). The levels of cytoskeletal proteins, Vimentin and Glial Fibrillary Acid Protein, were also studied. The effect of the pre-treatment with Indicaxanthin on cell viability, total Reactive Oxygen Species, superoxide anion and apoptotic pathway activation was assessed. Since Nestin is co-expressed in pluripotent stem cells with cyclin D1, their levels were also evaluated. Our findings highlight that Aβ (1–42) and its fragments induced an increase of TG2 levels and the different expression pattern of its isoforms on OECs. Indicaxanthin pre-treatment was able to reduce TG2 over-expression upregulated by Aβ exposure of cells differently modulating its isoforms. In addition, it prevented total Reactive Oxygen Species and superoxide anion production, it reduced Glial Fibrillary Acid Protein and Vimentin levels and inhibited apoptotic pathway activation. It also leaded to an increase of Nestin and cyclin D1 expression, stimulating stem cells renewal through the reparative activity played by TG2. Our results suggest that Aβ in OECs, both in the absence and in the presence of Indicaxanthin, might differently induce the transition of TG2 between “closed” and “open” conformation, providing a new mechanism involved in the signal pathways activated by the protein in Aβ injury important for neural regeneration of AD.