Protectin D1 also known as neuroprotectin D1 (when it acts in the nervous system) and abbreviated most commonly as PD1 or NPD1 is a member of the class of specialized proresolving mediators.

Like other members of this class of polyunsaturated fatty acid metabolites, it possesses strong anti-inflammatory, anti-apoptotic and neuroprotective activity.

Studies in Alzheimer's disease animal models, in stroke patients and in human retina pigment epithelial cells (RPE) have shown that PD1 can potentially reduce inflammation induced by oxidative stress and inhibit the pro-apoptotic signal, thereby preventing cellular degeneration.

[1] 15-LO-1 is a non-heme iron-carrying dioxygenase that adds oxygen atoms in a stereospecific manner on free and esterified ω-3 polyunsaturated fatty acids like DHA.

[2] These studies have proposed that PD1 acts as a signaling molecule and through its ligand-receptor interaction down-regulates the expression of genes, such as the transcription factor NF-κB.

[2] In addition, PD1 has an important role in regulating the expression of the Bcl-2 family proteins (Bcl-2, Bcl-xL, Bax and Bad) that precedes the release of the cytochrome c complex from the mitochondria and the formation of the apoptosome.

[4] Consequently, the activity of the Bcl-2 family proteins results in the inhibition of the caspase 3 enzyme, thus preventing apoptosis and promoting RPE cell survival.

[5] Specifically, PD1 in Alzheimer's disease models has been shown to respond to the increased concentration of the pro-inflammatory molecule Aβ42 by binding and activating the peroxisome proliferator-activated receptor gamma (PPARγ) either directly or via other mechanisms.

Overall, the above mechanism leads to the cleavage of βAPP protein though a non-amyloidogenic pathway that halts the formation of Aβ42 and prevents the premature neuronal degeneration.

Specifically, the NXF1 transporter through its middle and C-terminal domains binds to the phenylalanine/glycine repeats in the nucleoporins (Nups) that line the nuclear pore.

However, the administration of PD1 has shown that this lipid mediator specifically inhibits the binding of the viral RNA to NXF1, thus disrupting the proliferation of the virus.

[7] The large scale industrial production of PD1 is of great interest for pharmaceutical companies in order to harvest the potent anti-inflammatory and anti-apoptotic activities of this lipid mediator.

Removal of the two tert-butyldimethylsilyl ethers (TBS-protecting groups) is attained with an excess of TBAF in THF at 0 °C which produces a diol containing a conjugated alkyne.

While the omega oxidation of many bioactive fatty acid metabolites such as leukotriene B4, 5-HETE, 5-oxo-eicosatetraenoic acid (i.e. 5-oxo-ETE) results in a ~100-fold fall in their activity, the omega oxidized product of PD1 has been shown to possess potent ease exhibits potent anti-inflammatory and proresolving actions by inhibiting PMN chemotaxis in vivo and in vitro and decreased pro-inflammatory mediator levels in inflammatory exudates of an animal model at levels comparable to PD1.

An early study mistakenly used PDX instead of PD1 in attributing anti-replicative and clinically beneficial effects in viral influenza disease in a mouse model to PD1.

10-Epi-PD1 was detected in only a small amount in human PMN extracts but was more potent than PD1 or PDX in blocking the inflammatory response to zymosan A-induced murine acute peritonitis.