Lipids’ Importance on Cancer Therapy and Multiple Sclerosis Treatment

Myelin is the protective covering or sheath that protects nerve cells, and is composed of fatty acids and protein. Medical scientists and researchers have always considered myelin as metabolically inert. However, a recent study by researchers at the MD Anderson Cancer Center of the University of Texas Houston surprisingly found that it is dynamic.

This discovery is significant in the development of cancer and multiple sclerosis treatments, because myelin can be damaged by some drugs given in cancer chemotherapy. This damage has been called "chemobrain," which occurs in up to 70% of cancer patients undergoing certain types of chemotherapy. Chemobrain cause temporary or permanent impairment in memory and thinking.

The researcher's findings have been published last March 23 in the "Journal of Clinical Investigation" online issue.

Morell and Quarles have discussed the structure of myelin as having composed of proteins and fatty substances. Being sheathed around nerves, including those in the spinal cord and brain, myelin allows the rapid and efficient transmission of electrical neural impulses along nerve cells. Demyelination, or damage to the myelin sheath, occurs in diseases like multiple sclerosis and in certain types of cancer chemotherapy.

Cancer Biology assistant professor and study leader Dr. Jian Hu said that the research team discovered damage in mature myelin caused by a number of chemotherapy drugs. This, he adds, could be the most consistent effect of neurotoxicity from chemotherapy. He states that the study showed how the mature myelin substance is very dynamic, especially the lipid components. this disproves the decades- to centuries-old belief that mature myelin is very stable. With these findings, many scientists now think otherwise.

The study has shown how the lipids in mature myelin have a rapid turnover and need Qki or quaking, which is an RNA-binding protein substance, for them to be able to function normally. Depletion of Qki causes rapid demyelination, showing gradual neurologic deficits in experimental mice. Qki is a significant co-activator of neural signaling proteins known as PPAR, or peroxisome proliferator-activated receptors, which have a role to play in controlling the transcription of genes concerned with lipid metabolism, by working in conjunction with RXRs or retinoid X receptors.

The study team discovered how Qki interacts with the PPAR isoform known as RXR-alpha and PPAR-beta in order to modulate transcription. The team found this as a potentially new way of treating demyelination in patients with multiple sclerosis and in cancer chemotherapy cases.

Hu further revealed that treating mice that have been depleted with Qki with RXR-alpha and PPAR-beta agonists significantly alleviated neurological disability and prolonged their survival. He also added that the lesions of the specimens having primary progressive multiple sclerosis have been characterized with downregulation of lipid metabolism key activities that are associated with RXR-alpha /PPAR-beta and Qki.

The study has demonstrated and made the significant discovery of showing how continuous production of lipids is essential for the maintenance of mature myelin. It also highlighted the underrated role of the metabolism of lipids in diseases and cancer chemotherapy that cause demyelination or chemobrain.