Studio dei meccanismi molecolari alla base del coinvolgimento della proteina NEF di HIV-1 nella demenza associata ad HIV-1 (HAD)

During HIV-1 associated dementia (HAD), a variety of HIV-1-induced lesions of the central nervous system (CNS) has been described, including neuronal loss, but very little is known about the mechanisms that lead to this process. Among HIV-1 proteins, we analysed the role of Nef since it could alter some signal transduction pathways related to cellular proteins involved in neuronal differentiation, such as ALK (Anaplastic Lymphoma Kinase), thus contributing to explain some of the HAD features. Our data show that Nef alters ALK expression and interferes with the ALK signal transduction pathway, in particular by modifying the MMP-9 (Matrix MetalloProteinase-9) and MMP-2 (Matrix MetalloProteinase-2) pathways. Furthermore, Nef and ALK show a cumulative effect in the modulation of cytochines/chemokines and of proteins involved in their common transduction pathways, such as MAP-K