Targeting the NF-κB Pathway for Therapy of Ischemic Stroke

Abstract

Ischemic strokes occur when a major cerebral artery or its branches are occluded, resulting in activation of inflammatory processes that cause secondary tissue injury, breakdown of the blood–brain barrier, edema or hemorrhage. Treatments that inhibit inflammatory processes may thus be highly beneficial. A key regulator of the inflammatory process is the nuclear factor kappa B (NF-κB) pathway. In its active form, NF-κB regulates expression of proinflammatory and proapoptotic genes. The molecules that interact with NF-κB, and the subunits that compose NF-κB itself, represent therapeutic targets that can be modulated to decrease inflammation. This review focuses on our current understanding of the NF-κB pathway and the potential benefits of inhibiting NF-κB in ischemia-reperfusion injury of the brain.

New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses

“…Alternatively, targeting the transcription factors (NFKB/RELA or SP1) which govern a large part of the proteome network may be an adequate strategy. Recently, Howell and Bidwell [168] reviewed the potential benefits of targeting NF-κB in ischemia-reperfusion injury in the brain.…”

Isofuranodiene, a Natural Sesquiterpene Isolated from Wild Celery (Smyrnium olusatrum L.), Protects Rats against Acute Ischemic Stroke

“…NF-κB has an important role in impairment during brain ischemia. For example, hypoxia, ROS, and other inflammatory mediators activate NF-kB signaling, increase phosphorylation, and activate the NF-κB p65 subunit [25]. During cerebral ischemic-reperfusion, NF-κB is involved in many processes, e.g., apoptosis and inflammation, by regulating gene expression [26].…”

YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA

“…To investigate the downstream signaling pathways that participate in YTHDC1-mediated neuronal survival, we tested several potential signaling pathways involved in OGD-induced neuronal survival including NFκB, Akt and ERK signaling pathways 27,31,32 . Early reoxygenation (3 h) after OGD induced an obvious increase of phosphorylation of ERK (p-ERK), p65 (p-p65), and Akt at Ser473 (p-Akt-S473) as well as Thr308 site (p-Akt-T308).…”