CHAPTER 15: Role of P2X7 Receptor Signaling in the Treatment of Parkinson’s Disease and Other Neurodegenerative Disorders

Neurodegenerative diseases such as Parkinson’s disease (PD) and prion disease are characterized by protein aggregation and gliosis, including astrocytes and microglia. Currently, there is no treatment for prevention of disease progression. It has been well characterized that neuroinflammation caused by aberrant activation of glial cells may play a critical role in the pathogenesis of neurodegenerative diseases, and thus modulation of neuroinflammatory reactions may be a possible therapeutic strategy. In this context, we focus here on the P2X7 receptor (P2X7R), a cation‐selective ion channel gated by extracellular adenosine triphosphate, as a drug target for the modulation of neuroinflammation in PD. P2X7R is highly expressed in microglia in the central nervous system and has a pivotal role in the maturation and release of the powerful pro‐inflammatory cytokine interleukin‐1β (IL‐1β). Importantly, increased expression of IL‐1β correlates with the progression of PD, and up‐regulation of P2X7R expression is also observed in animal models of PD. Furthermore, evidence is accumulating to indicate that P2X7R may be involved in a variety of cellular events that lead to both neurodegeneration and neuroprotection. Thus, drugs that modulate P2X7R activity may provide a new strategy for treatment of Parkinson’s and other neurodegenerative diseases.