When glutamate accumulates...
In human cells, proteins called tubulins are assembled like bricks, forming microscopic tubes known as microtubules. These tubes then act like rails for transporting other elements. This is how chemical messengers are carried across large distances within a single nerve cell, the extension of which can run from the spinal cord to the tip of a toe. But as is often the case, the slightest anomaly can have serious consequences.
Researchers know that dysfunction in how microtubules are transported can result in neurodegenerative diseases such as Alzheimer’s, as well as a number of other pathologies. Carsten Janke and his team worked their way back up the chain of evidence to see whether the problem originated in the microtubules themselves. In mice, they discovered that microtubules were supplemented by tiny amino acids called glutamates.
A little glutamate is key to microtubules functioning as they should, but can be harmful in excessive amounts. They found that the gene tasked with controlling this ‘polyglutamylation’ was disrupted in children suffering from a serious and rare nervous system disease. In one mouse that displayed signs of this disease, the researchers were able to reverse the polyglutamylation process and improve its condition. It remains to be seen whether the same phenomenon is involved in other neurodegenerative diseases. Cellular biologists are working closely with neurobiologists to come up with answers to these questions.
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