Alzhèimer's 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, which induces intracellular calcium levels increase, oxygen reactive species production (ROS) and cell death. Several findings demonstrated that tissue Transglutaminase (TG2), an ubiquitary calcium-dependent protein that catalyzes the cross-linking of a wide spectrum of proteins including A?, is involved in protein aggregation in AD. In previous studies, we demonstrated that the treatment of Olfactory Ensheathing Cells (OECs), a particular glial cell type, with growth factors was able to reduce the aberrant expression of TG2 induced by A?. In the last years growing attention rose on neuronutraceutics, such as indicaxanthin, able to cross the blood brain barrier and modulate the bioelectric neuronal activity in the hippocampus. Indicaxanthin is a phytochemical produced by fruits included in the so-called "Mediterranean Diet", that has been proposed to be effective against cognitive decline associate to neurodegenerative diseases, e.g. AD. Herein, we assessed Indicaxanthin effect on TG2 overexpression induced by A?(1-42) native full-length peptide or by fragment A?(25-35) or A?(35-25) on OECs. The percentage of cellular viability by MTT test and the intracellular ROS levels were tested. The effect of Indicaxanthin on the expression levels of some cytoskeletal proteins, such as Vimentin, GFAP and Nestin through immunocytochemical analysis, was evaluated. The ability of Indicaxanthin to inhibit caspase-3 cleavage was also assessed. The pre-treatment with Indicaxanthin was able to restore the levels of the proteins to control values, and the intracellular oxidative status modified by the exposure to A?(1-42) or A?(25-35). Our data suggest that Indicaxanthin treatment might represent an innovative mechanism to contrast TG2 expression, which plays a key role in AD.
Protective effect of Indicaxanthin on tissue transglutaminase overexpression induced by Amyloid- beta exposure on Olfactory Ensheathing Cells
Rosalia Pellitteri
2019
Abstract
Alzhèimer's 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, which induces intracellular calcium levels increase, oxygen reactive species production (ROS) and cell death. Several findings demonstrated that tissue Transglutaminase (TG2), an ubiquitary calcium-dependent protein that catalyzes the cross-linking of a wide spectrum of proteins including A?, is involved in protein aggregation in AD. In previous studies, we demonstrated that the treatment of Olfactory Ensheathing Cells (OECs), a particular glial cell type, with growth factors was able to reduce the aberrant expression of TG2 induced by A?. In the last years growing attention rose on neuronutraceutics, such as indicaxanthin, able to cross the blood brain barrier and modulate the bioelectric neuronal activity in the hippocampus. Indicaxanthin is a phytochemical produced by fruits included in the so-called "Mediterranean Diet", that has been proposed to be effective against cognitive decline associate to neurodegenerative diseases, e.g. AD. Herein, we assessed Indicaxanthin effect on TG2 overexpression induced by A?(1-42) native full-length peptide or by fragment A?(25-35) or A?(35-25) on OECs. The percentage of cellular viability by MTT test and the intracellular ROS levels were tested. The effect of Indicaxanthin on the expression levels of some cytoskeletal proteins, such as Vimentin, GFAP and Nestin through immunocytochemical analysis, was evaluated. The ability of Indicaxanthin to inhibit caspase-3 cleavage was also assessed. The pre-treatment with Indicaxanthin was able to restore the levels of the proteins to control values, and the intracellular oxidative status modified by the exposure to A?(1-42) or A?(25-35). Our data suggest that Indicaxanthin treatment might represent an innovative mechanism to contrast TG2 expression, which plays a key role in AD.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
