
-   SerpinA3N expression in N42 in neurons is upregulated by palmitic acid and by leptin, together with *IL-6* and *TNF alpha*, and all three genes are downregulated by the anti-inflammatory monounsaturated fat, oleic acid. Additionally, palmitate upregulation of *serpinA3* in N42 neurons is blocked by the NF kappa B inhibitor, and upregulation of *serpinA3N* expression in the hypothalamus by HFD is blunted in IL-1 receptor 1 knockout (*IL-1R1* *^\-/^\-^* ) mice [PMID: 30519364].
-   Co-immunoprecipitation and Western blotting experiments established a direct interaction between SerpinA3N and RYR2 in the hippocampus of epileptic mice. This interaction leads to an increase in both total and phosphorylated RYR2, as shown by Western blotting. Immunofluorescence also indicated that this interaction predominantly occurs in astrocytes [PMID: 37422673].
-   RNA sequencing and Western blot analysis on hippocampal tissues from mice overexpressing SerpinA3N revealed a significant activation of the NF-kappa B signaling pathway. This was evidenced by increased expression of NF-kappa B and its phosphorylated forms. The application of Triptolide, an NF-kappa B inhibitor, further confirmed SerpinA3N's role in enhancing neuroinflammatory responses through this pathway [PMID: 37422673].
-   SerpinA3N reduces neuronal apoptosis and neuroinflammation by activating the Akt-mTOR pathway after stroke in the acute phase, as shown by co-immunoprecipitation-mass spectrometry and Western blotting experiments both in vitro and in vivo [PMID: 34897996].

## Summary

Serpina3n encodes a serpin family protein that inhibits serine proteases involved in inflammation and neuronal damage, such as cathepsin G, chymase, granzyme B, and neutrophil elastase [CS: 8]. Its protein product assists in maintaining vascular integrity by inactivating proteases that disrupt the blood-brain barrier (BBB) and reducing immune cell infiltration, thereby protecting neuronal tissue from inflammatory damage [CS: 8].

In response to brain injury or disease, the expression of Serpina3n is upregulated as part of the neuroinflammatory response mediated by cytokines like IL-6 [CS: 8]. This upregulation serves to curtail the harmful effects of enzymes released by activated immune cells, such as granzyme B and neutrophil elastase, which if uncontrolled could exacerbate BBB disruption and neuronal death [CS: 7]. In glioblastoma and neurodegenerative diseases like Alzheimer's, the increased presence of Serpina3n reflects an attempt to counteract the aggressive degradation of the extracellular matrix and protect neurons from excessive inflammation-induced apoptosis [CS: 6]. During incidents of brain trauma or ischemia, higher levels of Serpina3n help moderate the neuroinflammatory response by inhibiting deleterious proteolytic activity, ultimately aiming to preserve brain function and limit secondary injury [CS: 7].
