The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke

Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-?B signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines.

Automated summary

Stroke is a life-threatening condition and a major cause of disability. Cerebral ischemia triggers an inflammatory response involving various cytokines and inflammation-related agents. Progranulin (PGRN), a multifunctional protein, plays a critical role in physiological processes such as cell proliferation, inflammation, wound healing, and nervous system development. The mature form of PGRN has anti-inflammatory properties, while its derivative, granulin, induces pro-inflammatory cytokine expression. PGRN is significantly involved in brain tissue damage caused by conditions like cerebral ischemia, improving mood and cognitive disorders. It may also protect against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis, as well as regulating microglia. PGRN acts as a neurotrophic factor in the central nervous system, promoting neurogenesis in the subventricular zone (SVZ) and improving long-term brain function after cerebral ischemia. The induction of PI3K/AKT and MAPK/ERK signaling pathways may contribute to PGRN-enhanced neurogenesis in the ischemic brain SVZ. Furthermore, PGRN can enhance the proliferation of neural stem/progenitor cells through the PI3K/AKT pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. Overall, PGRN is a potent neuroprotective agent that improves post-ischemia neuronal function by modulating inflammatory and anti-inflammatory cytokines.