Molybdenum Cofactors Toward Treating Neurological Diseases

Molybdenum cofactor (Moco) is a compound that is little known but is essential for life. Children born without the ability to synthesize Moco die young of neurological diseases. It has not been possible to create Moco supplements because the compound is so unstable. Studies in the nematode Caenorhabditis elegans suggest that by combining, Moco with certain proteins, it becomes stable and can repair deficiency of human neurological diseases.

Studies with a popular laboratory model, the nematode Caenorhabditis elegans, have revealed a possible therapeutic avenue for a rare but deadly condition in which children are born without the ability to make molybdenum cofactor (Moco) on their own. Though little known, Moco is essential for life and so far it has proven extremely difficult to stably isolate this compound in the laboratory, preventing its use as a therapeutic supplement.

This new work, which appears in Genes & Development, reveals that nematodes genetically engineered to be Moco-deficient can take up Moco that is attached to several types of proteins. This suggests that such protein-Moco complexes could be used as a treatment for Moco deficiency.

Children born with mutations that make them unable to synthesize Moco suffer lethal neurological diseases. Providing them supplemental Moco might reverse these devastating symptoms. Moco is vital to life. So far, it has proved extremely difficult to isolate this compound stably in the laboratory, which makes it difficult to use it as a therapeutic supplement as a treatment option.

Researchers conducted studies in Caenorhabditis elegans, which are designed to lack the ability to make Moco. Like humans, Caenorhabditis elegans deficient in Moco die very early in development. Nematodes, however, can also ingest Moco from their diet, a process that is similar to supplementation, as with vitamins. The researchers found that the worms could take in Moco as a range of purified Moco-protein complexes. These included complexes with proteins from bacteria, bread mold, green algae and cow's milk. Ingesting these complexes saved the Moco-deficient worms.

Further, they demonstrated that the Moco-protein complexes were very stable, suggesting it is possible to produce them as a supplement for children born with Moco deficiency.

One of the paper's author stated that they tested four proteins and all four were restorative in the nematode model. The results relate to patients, the researchers are extremely excited about the therapeutic and fundamental implications of the molybdenum cofactors for treating neurological diseases.

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