First 50 Blogs

Plasmalogens are a unique class of phospholipids that contain a vinyl-ether bond at the sn-1 position on the glycerol backbone and this double bond gives this lipid class important characteristics. Research into plasmalogens began in 1924 when Feulgen and Voit attempted to stain tissue sections with acid or mercuric chloride to stain the nucleus but ended up breaking the vinyl-ether bond, producing aldehydes. Since then, we have gone on to learn about the importance of plasmalogens in membrane structure and fluidity, lipid raft organization, vesicular fusion, and antioxidative properties. This range of roles makes it unsurprising that many disorders are associated with a reduction in plasmalogen levels, including Parkinson’s disease, multiple sclerosis, and Alzheimer’s disease (AD). In extreme cases when a person is unable to synthesize plasmalogens this results in rhizomelic chondrodysplasia punctata (RCDP). RCDP is a genetic disorder that causes severe form of dwarfism and cognitive deficits characterized by stunted growth, shortened proximal bones, cataracts, seizures, and recurrent respiratory illness. Studies have been ongoing to determine the roles of plasmalogens in our cells and bodies and whether plasmalogens or plasmalogen-precursor treatments can provide any benefit to a plasmalogen deficiency.

Plasmalogen research is an active field with new discoveries consistently being made. Some notable work that we have highlighted in our literature blogs include the discovery of TMEM189, a gene that encodes plasmanylethanolamine desaturase, the enzyme responsible for introducing the vinyl-ether bond in the plasmalogen biosynthetic pathway, by Werner et al. As well, the location of two other enzymes in the final step of this pathway was confirmed by Horibata et al. An update on the morbidity and mortality of RCDP was also published recently. In 2019 Duker et al reported that the 5 year survival of RCDP was 75%, a great increase from the 60% probability reported in 2003 for these children. Duker et al also described that the most significant factor in survival rate of RCDP is plasmalogen level, where those with “classic” RCDP and nearly undetectable levels of plasmalogens having a lower survival probability than those with “non-classic” RCDP and higher levels of endogenous plasmalogens. AD, a neurodegenerative disease characterized by memory loss and cognitive decline, has also been a common disease focused on in plasmalogen research. Spears et al looked at the link between vascular plasmalogens and neurodegeneration and found that an endothelium knock-out of plasmalogens in the vasculature lining had a strong enough effect to alter plasma levels and cause memory deficits in the mice. Uruno et al used an amyloid precursor protein (APP) knock-in mouse model to observe oxidative stress and inflammation in the model and demonstrated the role of plasmalogens in some of the memory-loss effects seen in AD, as well as suggesting a new therapeutic target to prevent plasmalogen reduction.

In addition, the literature blog explored the association between plasmalogens and lesser-known diseases including Barth syndrome (BTHS), a rare genetic disorder characterized by muscle weakness, an enlarged heart, and mitochondrial dysfunction, and Gaucher disease, an autosomal disorder that causes fat build up in macrophage lysosomes. Bozelli et al analyzed lymphoblasts derived from BTHS patients treated with plasmalogen precursors and found that the treatment normalized cell viability, mitochondrial biogenesis and mitochondrial membrane potential. Moraitou et al focused on Gaucher disease and stated that plasmalogen deficiency may increase oxidative stress and cause additional α-synuclein accumulation. Gaucher disease is one of the risk factors for Parkinson’s disease and the plasmalogen deficiency may be the link between the two.

There has been plenty of research geared towards developing therapies to increase plasmalogen levels through direct plasmalogen supplementation or by administering a plasmalogen precursor. These include the use of eicosapentaenoic acid (EPA)-enriched ethanolamine plasmalogens, batyl alcohol, plasmalogens isolated from egg yolk or ascidian viscera, docosahexaenoic acid, shark liver oil, plasmalogens isolated from scallops, and alkylglycerol mix. Many of the different treatments demonstrated a benefit in the cell and animal models tested and provide support for the use of plasmalogens or plasmalogen precursors in treating a range of ailments from AD to cardiac conduction to ischemic stroke to normalizing levels in a plasmalogen deficiency model.

Since this literature blog launched 18 months ago, there have been some incredible findings in plasmalogen research. Every year more work is being done with plasmalogens to better understand their role in cells, in disease, and their efficacy as therapeutics. Although we have covered many topics over these last 50 blog posts, there are many articles that we have not described yet, and more discoveries are published every day. We look forward to seeing what we will discover and learn in the next 50!