ASTAXANTHIN EFFECT ON TISSUE TRANSGLUTAMINASE EXPRESSION IN OLFACTORY GLIA EXPOSED TO AMYLOID-?

Alzheimer Disease (AD), one of the most common neurodegenerative diseases, is characterized by progressive neuronal loss and accumulation of proteins, including Amyloid-beta (A?), a neurotoxic protein. 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 and its isoforms on Olfactory Ensheathing Cells (OECs), a glial population of the olfactory system expressing neural stem cell markers, including Nestin. In the last years growing attention rose on neuronutraceutics and their effect on mental health, as many compounds are characterized by antioxidant and anti-inflammatory activities, these properties could have beneficial effects in counteracting the multifactorial onset and progression of AD. Among these molecules, we focus on Astaxanthin, a natural compound predominantly found in marine organisms, the green microalgae Haematococcus pluvialis and Chlorella zofingiensis; it can be transported into the brain through the blood-brain barrier and exhibits powerful anti-oxidant activity. In addition, Astaxanthin can effectively scavenge intracellular free radicals and destroy peroxide chain reactions, protecting cell and biological membranes from oxidative damage. Therefore, it exhibits numerous health benefits, such as anti-inflammatory actions, anti-tumor effects, hepatoprotective effects, and immunomodulatory activity. In this study, the effect of Astaxanthin pretreatment on TG2 and its isoform expression exposed to A?(1-42) or by A?(25-35) or A?(35-25) on OECs was assessed. Moreover, we evaluated Astaxanthin effect on the expression of some cytoskeletal proteins, Vimentin, Glial Fibrillary Acid Protein (GFAP), Nestin and Caspase-3. Astaxanthin pre-treatment reduced TG2 overexpression, modulating the level of TG2 isoforms and reduced ROS production, GFAP and Vimentin expression, inhibiting apoptotic pathway activation and induced an increase in the Nestin levels. Our data demonstrated that Astaxanthin pre-treatment stimulated OECs self-renewal through the reparative activity played by TG2. Therefore, pre-treatment Astaxanthin might represent an innovative mechanism to contrast TG2 overexpression in AD.