Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Its neuropathological hallmarks include deposition of beta amyloid (Aβ) fibrils in senile plaques. Thus, since inflammatory process and oxidative stress are considered to play an important role in neuroinflammatory disorders and in AD pathology, in the present work we decided to test a new composite, which is a formulation constituted of an anti-inflammatory compound such as palmitoylethanolamide (PEA) and the well recognized antioxidant flavonoid luteolin (Lut), subjected to an ultra-micronization process, co-ultraPEALut. We investigated the effect of co-ultraPEALut in both an in vitro and ex vivo organotypic model of AD. For the in vitro model, we used human neuronal cells, obtained by differentiating SH-SY5Y neuroblastoma cells into sustainable neuronal morphology. Differentiated SH-SY5Y cells, were pre-treated with co-ultraPEALut (reference concentrations: 27, 2.7 and 0.27 μM PEA) for 2 h. AD features were induced by Aβ1-42 stimulation (1 µM). Twenty-four hours later cell vitality was evaluated by MTT assay, whereas the neuroinflammation underling AD were observed by Western blot analysis for IκBα degradation and nuclear factor-κB traslocation, as well as GFAP expression. For organotypic model of AD, hippocampal slice cultures were prepared from mice at postnatal day 6 and after 21 days of culturing the slices were pre-treated with co-ultraPEALut (reference concentrations: 27, 2.7 and 0.27 μM PEA) for 2 h and then incubated with Aβ1-42 (1 μg/ml) for 24 h. Pre-treatment with co-ultraPEALut significantly reduced inducible nitric oxide synthase (iNOS) and GFAP expression, restored neuronal nitric oxide synthase (nNOS) and brain-derived neurotrophic factor (BDNF) and reduced the apoptosis process. Taken together our results clearly showed that co-ultraPEALut is able to blunt Aβ-induced astrocyte activation and to exert a marked protective effect on glial cells. These findings suggest that the association of co-ultraPEALut may provide an effective strategy for AD.

Neuroprotection by association of palmitoylethanolamide with luteolin in experimental alzheimer’s disease models: the control of neuroinflammation

Cordaro Marika;Paterniti Irene;Campolo Michela;Siracusa Rosalba;Navarra Michele;Cuzzocrea Salvatore;Esposito Emanuela
2014-01-01

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Its neuropathological hallmarks include deposition of beta amyloid (Aβ) fibrils in senile plaques. Thus, since inflammatory process and oxidative stress are considered to play an important role in neuroinflammatory disorders and in AD pathology, in the present work we decided to test a new composite, which is a formulation constituted of an anti-inflammatory compound such as palmitoylethanolamide (PEA) and the well recognized antioxidant flavonoid luteolin (Lut), subjected to an ultra-micronization process, co-ultraPEALut. We investigated the effect of co-ultraPEALut in both an in vitro and ex vivo organotypic model of AD. For the in vitro model, we used human neuronal cells, obtained by differentiating SH-SY5Y neuroblastoma cells into sustainable neuronal morphology. Differentiated SH-SY5Y cells, were pre-treated with co-ultraPEALut (reference concentrations: 27, 2.7 and 0.27 μM PEA) for 2 h. AD features were induced by Aβ1-42 stimulation (1 µM). Twenty-four hours later cell vitality was evaluated by MTT assay, whereas the neuroinflammation underling AD were observed by Western blot analysis for IκBα degradation and nuclear factor-κB traslocation, as well as GFAP expression. For organotypic model of AD, hippocampal slice cultures were prepared from mice at postnatal day 6 and after 21 days of culturing the slices were pre-treated with co-ultraPEALut (reference concentrations: 27, 2.7 and 0.27 μM PEA) for 2 h and then incubated with Aβ1-42 (1 μg/ml) for 24 h. Pre-treatment with co-ultraPEALut significantly reduced inducible nitric oxide synthase (iNOS) and GFAP expression, restored neuronal nitric oxide synthase (nNOS) and brain-derived neurotrophic factor (BDNF) and reduced the apoptosis process. Taken together our results clearly showed that co-ultraPEALut is able to blunt Aβ-induced astrocyte activation and to exert a marked protective effect on glial cells. These findings suggest that the association of co-ultraPEALut may provide an effective strategy for AD.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3145106
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