Therapeutic Potential of PCSK9 Inhibitors in Regulating Neuroinflammation in Acute Ischemic Stroke - PubMed
3 hours ago
- #acute ischemic stroke
- #neuroinflammation
- #PCSK9 inhibitors
- Acute ischemic stroke (AIS) is a major cause of disability and death, with neuroinflammation contributing to secondary brain damage.
- PCSK9, known for cholesterol metabolism, also mediates neuroinflammation, making it a potential therapeutic target.
- PCSK9 disrupts mTOR pathways, activating inflammatory cascades (NF-κB, TLR4, MAPK) in microglia and increasing cytokine release (IL-1β, IL-6, TNF-α).
- PCSK9 interacts with ApoER2 on neurons and indirectly increases Lp(a), promoting inflammation via the Lp(a)-TLR4 axis.
- PCSK9 inhibitors (e.g., evolocumab, alirocumab, inclisiran) reduce neuroinflammation by blocking microglia M1 polarization and downregulating pro-inflammatory factors.
- These inhibitors also protect the blood-brain barrier (BBB), inhibit neuronal apoptosis, and reduce β-amyloid aggregation.
- Preclinical and clinical studies show PCSK9 inhibitors lower LDL-C, Lp(a), and systemic inflammatory markers (e.g., hs-CRP, IL-6).
- Early use of evolocumab in AIS reduces neurological deterioration, indicating benefits beyond lipid lowering.
- Future research should focus on optimizing therapeutic windows, improving BBB penetration, and refining patient stratification.