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 (p75NTR) 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/p75NTR/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/p75NTR/sortilin signaling pathway could be a promising therapeutic strategy in the management of AIS.