Dysregulation of proBDNF/p75NTR and BDNF/TrkB Signaling in Acute Ischemic Stroke: Different Sides of the Same Coins

Acute ischemic stroke (AIS) is a focal neurological deficit due to sudden occlusion of cerebral vessels in the brain. AIS-induced neuronal injury and associated excite-toxicity and neurodegeneration affect the synthesis and the release of different neurotrophic factors such as brain-derived neurotropic factor (BDNF) and its precursor proBDNF. Both BDNF and proBDNF act on the specific receptors with different neurological effects. BDNF activates tropomyosin receptor kinase B (TrkB) receptor results in promoting neuronal survival, synaptic plasticity, and neuronal growth. However, the proBDNF activates p75 neurotrophin receptor (p75 NTR ) and sortilin which attenuates synaptic plasticity and promotes neuronal apoptosis. Dysregulation of central and peripheral expression of proBDNF/BDNF is linked with the severity and clinical outcomes of AIS. Therefore, this review aims to discuss the alterations of proBDNF/BDNF signaling in AIS. Findings from the present review illustrated that proBDNF/p75 NTR /sortilin signaling pathway is exaggerated whereas; BDNF-TrkB signaling is reduced in AIS leading to neuronal apoptosis. Therefore, activation of BDNF-TrkB signaling, and inhibition of proBDNF/p75 NTR /sortilin signaling pathway could be a promising therapeutic strategy in the management of AIS. • Acute ischemic stroke affect BDNF and its precursor, proBDNF, signaling. • BDNF signaling induces neuronal survival, synaptic plasticity, and neuronal growth. • proBDNF signaling attenuates synaptic plasticity and promotes neuronal apoptosis. • proBDNF and BDNF signaling balance is important for the brain integrity. • Targeting proBDNF and BDNF signaling in acute ischemic stroke could be beneficial.