Alzheimer’s disease (AD) is a neurodegenerative disease caused by poorly known pathogenetic mechanisms and aggravated by delayed therapeutic intervention; it still lacks an effective cure. However, it is clear that some important neurophysiological processes are altered years before the onset of clinical symptoms, offering the possibility of identifying biological markers useful for early diagnosis and implementation of effective therapies. It has become clear over recent years that nonneuronal cells, mainly microglia, are dysfunctional in the AD brain, and that inflammation of the brain (neuroinflammation) has a very important pathogenic role.
A key molecule involved in the activation and propagation of inflammation is ATP. ATP is well known for being the fundamental intracellular energy currency; however, we now know that this molecule also is released into the extracellular space when cells are stressed or injured. In the tissue interstitium, extracellular ATP (eATP), is a signal of danger to nearby cells, thus acting as a “damage-associated molecular pattern” (DAMP). At sites of inflammation, eATP accumulates at high concentrations and stimulates specific receptors named P2 purinergic receptors, P2X7 being the subtype most frequently involved, thus promoting secretion of other DAMPs and pro-inflammatory cytokines.
We aim at investigating the role played by the eATP/P2X7 receptor pathway in the promotion of microglia dysfunction and in AD-associated neuroinflammation. Our final goal will be to validate eATP/P2X7 as novel potential therapeutic targets and/or early diagnostic markers in AD.