ROLE OF NATURAL ANTIOXIDANTS ON TISSUE TRANSGLUTAMINASE LEVELS IN GLIAL OLFACTORY CELLS EXPOSED TO AMYLOID-Β: INTEGRATED BIOCHEMICAL AND COMPUTATIONAL STUDY

Several findings report the protective effect exerted by nutraceuticals on the health of the nervous system, since many compounds are characterized by antioxidant and anti-inflammatory activities. Alzheimer Disease (AD) is characterized by an aberrant accumulation of amyloid-β (Aβ) responsible of neurotoxicity. Our research focuses on the interaction between some natural antioxidants (berberine and curcumin) and tissue transglutaminase (TG2) levels, in the absence and in the presence of amyloid-β (Aβ) in Olfactory Ensheathing Cells (OECs), a glial cell type of olfactory system. TG2 is an ubiquitarian calcium-dependent protein, involved in AD. Docking studies were performed to ascertain the binding affinity of compounds against the TG2 closed and open forms. In the biological investigation, the effect of berberine and curcumin treatment on TG2 levels in OECs exposed to Aβ was tested. Cell viability, cytoskeleton marker (GFAP, vimentin and nestin) expression, reactive oxygen species (ROS) and apoptotic pathway activation were assessed. Our results demonstrate that pretreatment of OECs with berberine or curcumin counteracted the Aβ-induced upregulation of TG2, restoring its expression to control levels. Furthermore, antioxidant pretreatment reinstated cell viability, normalized the expression of GFAP, vimentin, and nestin, reduced intracellular ROS accumulation, and prevented activation of the apoptotic cascade. The computational data were in quite agreement with biological results. Our findings highlight that berberine and curcumin are able to exert a protective effect against Aβ toxicity in OECs. Therefore, they might represent a promising tool for neural regeneration and for potential therapy slowing or preventing the progression of AD.