Fancello, Silvia (2019) Sviluppo di strategie per nuovi approcci terapeutici nelle malattie neurodegenerative. Doctoral Thesis.
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Development of strategies for new therapeutic approaches in neurodegenerative diseases
Nowadays the causes of the onset of neurodegenerative diseases are not completely yet known, but it is confirmed that environmental, metabolic and nutritional factors contribute to their development. Among the involved mechanisms in neurodegeneration, the oxidative stress has been extensively studied in recent decades. In this regard in the present work, various drug delivery systems have been tested, as such or containing drugs, to evaluate their pharmacological effect in different cell models. Molecules of different nature, loaded to transferosomes or chitosan particles, protected PC12 cells from oxidative damage induced by hydrogen peroxide and from parkinsonism induced by the neurotoxin MPTP. A further study on MPTP damage was performed to measure glucose and lactate levels involved in the energy metabolism of cells using enzymatic biosensors. The cells were exposed to insulin, hormone known in literature to promote glucose internalization, which was able to restore aerobic metabolism interrupted by the damage induced by neurotoxin. The promising results obtained in this research allows to hypothesize new therapeutic approaches, based on drug delivery systems and drugs already known in several roles, able to protect as co-therapeutics in neurodegenerative diseases, such as Parkinson.
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