Researchers at Tel Aviv University, Israel, have elucidated several aspects of the function of an organic compound which holds promise in therapies against neurodegenerative diseases such as Alzheimer’s, Parkinson’s, schizophrenia and Amyotrophic lateral sclerosis (ALS). The study, published in the journal Neurobiology of Disease, shows that administration of this compound to mouse models of ALS treated most of symptoms and prolonged the lifespan.
Microtubules are, as the name reveals, hollow elongated tubes which reside inside all of our cells. They provide the scaffold and support (like our skeleton); they separate chromosomes when cells divide; they provide the roadway for proteins and other organelles to move from one side of the cell to the other. Microtubules are important for all of our cells, bu they are especially important for neurons.
Let’s take one of our one hundred billion neurons in our body. The job of each one of them is to transfer signals and molecules from the brain to other cells and vice versa. This is achieved by the shape of the neuron cell, which extends axons from its main body. In fact, we have axons that can be as long as our entire body is. The interior of each axon is made of microtubules on which molecules travel. Therefore, malfunctioned microtubules can cause severe neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Alzheimer’s or Parkinson’s disease.
Professor Illana Gozes, director of the Adams Super Center for Brain Studies, has created a peptide (a small part of a protein) which resembles a protein termed activity-dependent neuroprotective protein (ADNP). ADNP is vital for brain formation and cognitive (mental) function of mammals. People presenting memory loss e.g. with schizophrenia, Alzheimer’s etc have little or malfunctioned ADNP in their brains. But the neuroprotective drug NAP can reverse some these effects in mice. It is not known yet how NAP exerts its functions but Gozes thought that it has something to do with stabilizing the microtubules.
In this new study, Dr. Yan Jouroukhin and his colleagues in Gozes’ lab used mouse models of ALS, which have damaged microtubules. The neurons of these mice do not transfer signals to and from the brain very effectively; the brain activity is severely damaged, thus they have mobility problems and live less than normal mice. The research team injected mice with different doses of NAP and immediately saw that the neurons of ALS mice are able to transport molecules as effective as healthy mice. The same were the results in the overall mobility tests of ALS mice. Also, postmortem analysis of the brains showed that NAP protected against brain and spinal cord damage. Last but not least, NAP treatment prolonged the lifespan of ALS mice significantly, especially of female mice.
This study puts together very useful information on the compound NAP, not only for ALS, but for other neurodegenerative diseases as well. The human and mouse ADNP are about 90% identical, and therefore very likely to have the same functions in the human body. In addition, as Gozes says in their paper, NAP presents a clean toxicology profile, whereas side effects are anticipated with other neuroprotective drug candidates affecting MT. This in itself makes NAP a good choice for a future neuroprotective drug.