Analisi dei cambiamenti dell'espressione proteica nell'ippocampo a seguito della sovraespressione del recettore 2A dell'adenosina in un nuovo topo modello

Alzheimer's disease is the most common neurodegenerative disease worldwide and different studies suggest that many lifestyle-related factors are involved in the onset of the disease. A crucial role in Alzheimer's disease and other neuropsychiatric conditions is played by adenosine receptors. In particular, adenosine is known to be involved in several functions like signalization, energy transfer, redox control, but primarily it is required in case of adverse metabolic conditions like hypoxia. Adenosine is a ubiquitous molecule, particularly abundant in the brain, where A1 and A2A receptors play a major role. It has been shown that these two receptors are involved both in neuroprotection and neurodegeneration. A1R seemed to be a promising endogenous neuroprotective system, but it has been demonstrated that its neuroprotective effect is lost after the occurrence of noxious stimuli and in case of prolonged insults it undergoes desensitization. A2AR studies, on the other hand, show that both genetic and pharmacological blockade has a strong neuroprotective role, and this makes it an ideal therapeutic target. To better study the effects of A2AR a new transgenic mouse model has been created, overexpressing A2AR in hippocampal neurons, known to be affected in Alzheimer's disease. In this study, that I performed during the Erasmus Traineeship at the Inserm laboratory in Lille, the effects of A2AR overexpression have been evaluated focusing on seven proteins of interest, previously selected by gene ontology analysis, to better understand the mechanisms involved during neurodegeneration but also to look for new molecular markers that could represent new therapeutic targets.