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The protein that fights Alzheimer’s and autism. Interview with Cristina Alberini

The protein that fights Alzheimer’s and autism. Interview with Cristina Alberini

30/06/2015

There’s a protein that improves memory function and has potential applications in diseases- like Alzheimer’s - as well as in other degenerative pathologies such as autism.  Cristina Alberini, a professor at New York University is studying the biological mechanisms that lead to the formation of new memories.  In 2011, she identified the effects that the protein, known as IGF-II and is produced by the brain, can have on long term memory. Today, her research continues with experiments on the active mechanisms governed by this molecule.

What is IGF-II and what effects can it have on the brain?
Insulin-like Growth Factor II, usually abbreviated to IGF-II, is a protein produced naturally by the brain and is essential to the formation of long term memory; put simply, the brain produces more IGF-II whenever it learns something new.  In the experiments we have carried out on mice, we have, amongst other things, administered a larger amount of this protein following a learning experience and this resulted in a significant improvement in memory function as well as greater persistence.  When, on the other hand, we blocked the endogenous increase of IGF-II produced by the learning experience, we observed that no long term memories were formed.  

What are the consequences of this discovery?
Our experiments have not only shown us that the protein produced by the brain is essential to the production of long term memory, but also that increasing the amount administered increases the length of time those memories endure and slows down the rate at which they are lost over time.  For now, we have only studied the effects on animals, but its potential usefulness to humans is also significant.

IGF-II’s potential usefulness is also linked to that fact that we have noted that this protein does not change the brain’s capacity for further learning; in other words, IGF-II increases memory function whilst the flexibility of the brain remains the same.  During our experiments, in fact, we also confirmed that enhancing memories had no negative effects at all on any new learning experiences, or in the elasticity with which previously learned memories were treated.

What are the potential applications of IGF-II?
Levels of IGF-II are raised in the hippocampus, the part of the brain that is important in the formation of long term memory, and this acts on the classic type of human memories that are described as explicit or declarative, whilst those of an emotive nature are not affected at all. It is, therefore, one of the areas of the brain most affected by the type of memory loss associated with aging, as in Alzheimer’s.

And that’s not all: amongst the memories affected by IGF-II, are those linked to overcoming fears.  If someone has a negative experience in a particular context, by re-exposing them several times to the same situation but without the fear factor, that fear can be completely extinguished.  It’s a strategy often used to treat phobias, and using IGF-II during that kind of treatment may help speed up and improve the process.  

It might also have a therapeutic effect in treating autism.  In normal mice, IGF-II improves the memory process associated with social recognition and in mice with some of the characteristics of autism, the protein was seen to recoup deficits typical of this condition.

Does this protein also improve the memory of healthy people?
IGF-II undoubtedly improves memory, and the flexibility and reversibility of the brain to learn.  Personally, however, I believe that it would be best used in cases of disease and illness before we start looking at its potential to improve the memory of healthy individuals.

The only potential obstacle we face is that because IGF-II is a known protein and is produced endogenously by the brain, the pharmaceutical industry may decide not to fully develop it because any useful discoveries resulting from this molecule that might, in due course, be made, could not be protected by a patent.  This would be a great shame as we can already see truly exceptional results in our animal experiments.  Older mice, for example, have the same memory problems as we humans, but administering IGF-II results in a significant improvement.

What is more, this protein passes through the blood brain barrier, a natural protective device that isolates the brain that really is a major obstacle as far as administering drugs is concerned.  It means that IGF-II provides a natural delivery system that can get to the brain and is easy to administer subcutaneously and probably intranasally too. 

 

Cristina Alberini is a Full Professor at the Center for Neural Science (CNS) at New York University. Her research has contributed to the characterization of the biological mechanisms needed to form and retain long term memories.  The particular focus of her research has been the identification of genes and proteins regulated by learning and that are necessary for the formation of long term memories, as well as the relationship between stress and memory and mechanisms that can enhance memory and prevent cognitive deterioration.