Extracellular Vesicles and Purinergic Signaling in Alzheimer's Disease-Joining Forces for Novel Therapeutic Approach

Neurodegenerative diseases, including Alzheimer's disease (AD), are a global problem affecting millions of people. Thanks to years of research and huge efforts, it has been possible to discover the pathophysiological changes accompanying Alzheimer's disease at the cellular level. It turns out that the formation of amyloid-beta plaques and hyperphosphorylation of tau protein in the brain play a key role in disease development. Purinergic signaling (PS) is implicated in the pathophysiology of several disorders in the central nervous system, and recent findings link some disturbances in PS with Alzheimer's disease. The primary objective of our review is to comprehensively explore and identify key purinergic signaling targets that hold therapeutic potential in the treatment of patients suffering from the disease. In particular, we focus on the dual role of purinergic compounds and extracellular vesicles (EVs), which have emerged as critical components in cellular communication and disease modulation. The extracellular vesicles that are naturally released by various cells fulfill the role of communication tools, also by harnessing the purinergic compounds. In this context, our review presents a thorough and integrative analysis of how extracellular vesicles can influence purinergic signaling and how this interaction might be leveraged to develop novel, targeted treatment strategies. Ultimately, this line of research may lead to innovative therapeutic approaches that are not only effective in slowing or halting disease progression but also demonstrate a high degree of biocompatibility and safety for the human organism.