Title:P2X7 Receptor-Associated Programmed Cell Death in the Pathophysiology of Hemorrhagic Stroke
Volume: 16
Issue: 9
Author(s): Hengli Zhao, Yujie Chen*Hua Feng
Affiliation:
- Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing,China
Keywords:
P2X7 receptor, apoptosis, autophagy, necroptosis, pyroptosis, intracerebral hemorrhage, subarachnoid
hemorrhage.
Abstract: Hemorrhagic stroke is a life-threatening disease characterized by a sudden rupture of
cerebral blood vessels, and cell death is widely believed to occur after exposure to blood metabolites
or subsequently damaged cells. Recently, programmed cell death, such as apoptosis, autophagy,
necroptosis, pyroptosis, and ferroptosis, has been demonstrated to play crucial roles in the
pathophysiology of stroke. However, the detailed mechanisms of these novel kinds of cell death are
still unclear. The P2X7 receptor, previously known for its cytotoxic activity, is an ATP-gated, nonselective
cation channel that belongs to the family of ionotropic P2X receptors. Evolving evidence
indicates that the P2X7 receptor plays a pivotal role in central nervous system pathology; genetic
deletion and pharmacological blockade of the P2X7 receptor provide neuroprotection in various
neurological disorders, including intracerebral hemorrhage and subarachnoid hemorrhage. The
P2X7 receptor may regulate programmed cell death via (I) exocytosis of secretory lysosomes, (II)
exocytosis of autophagosomes or autophagolysosomes during formation of the initial autophagic
isolation membrane or omegasome, and (III) direct release of cytosolic IL-1β secondary to regulated
cell death by pyroptosis or necroptosis. In this review, we present an overview of P2X7 receptor-
associated programmed cell death for further understanding of hemorrhagic stroke pathophysiology,
as well as potential therapeutic targets for its treatment.
