What is huntingtin for?
Huntington's Disease Protein is needed for proper brain development
Kirill Stasevich, "Science and Life" based on Duke University: Huntington's Disease Protein Helps Wire the Young BrainWithout the normal huntingtin protein, synapses in the developing brain are first rapidly formed, and then just as rapidly destroyed.
Huntington's disease, like other neurodegenerative diseases, develops due to the mutant huntingtin protein. The mutation makes this protein toxic, neurons begin to die, which manifests itself in a variety of symptoms: it becomes difficult for a person to control movements, memory and concentration ability deteriorate, depression and aggressiveness increase. As usually happens with such diseases (which include Alzheimer's syndrome and Parkinson's syndrome), obvious mental symptoms appear when the brain is already severely affected.
However, a few years ago, neuroscientists from Duke University suddenly discovered that the Huntington's disease protein is involved in the formation of new synapses. In general, until now, the normal functions of huntingtin are known only in the most general terms, so the researchers took the opportunity and tried to study its effect on the developing brain more deeply. To do this, the protein gene was turned off in the cortex of mice and then they looked at what would happen to neurons at different stages of development.
At the third week of birth (which roughly corresponds to a two-year–old child), mice had a "synaptic explosion" in the brain - connections between neurons were formed extremely actively. Obviously, such a reaction of neurons is associated with a huge flow of visual and auditory information that begins to enter the animal's brain at this age. However, in mutant mice deprived of huntingtin, the formation of new interneuronal contacts went much faster than in normal mice.
By the fifth week, editing of synapses began: some of them intensified, some weakened and disappeared altogether. Such a redistribution of interneuronal contacts is necessary for proper brain tuning – neurons get rid of unnecessary connections and thereby optimize the information flows that pass through them. In ordinary, non-mutant mice, this process went as it should. But in animals with huntingtin turned off, most synapses were degraded, regardless of how much they are needed or not needed by the brain.
Moreover, the absence of protein put the cells under stress, which was especially noticeable in the area of the cortex that exchanged data with the striatum. The striatum, or striatum, is needed for muscle control, complex motor reactions and reflexes. In Huntington's disease, the striatum is one of the first to suffer, but, taking into account new data, we can say that the striatum in general strongly depends on the huntingtin protein and therefore reacts strongly to everything that happens to this protein. Its absence plunges striatum cells into stress, on the other hand, a mutation in huntingtin triggers neurodegenerative processes here.
The absence of the huntingtin protein causes stress in the service cells of the brain –
astrocytes (green) and microglial cells (white and red).
(Photo by Spencer McKinstry / Duke University).
But the following turned out to be even more curious: when Huntington's disease itself was provoked in mice, that is, when neurons were forced to synthesize a mutant protein, the picture with synapses turned out to be the same as in the absence of protein – synapses were first overactive formed, and then rapidly destroyed. It turns out that huntingtin is needed to support synapses. And it should be in a normal, non-mutant form (after all, strictly speaking, its pathogenic properties appear only after mutation). The results of the experiments were published by the authors in the Journal of Neuroscience (McKinstry et al., Huntingtin Is Required for Normal Excitatory Synapse Development in Cortical and Striatal Circuits – VM).
This is not the first time that important and useful functions have been found in proteins involved in neurodegenerative processes. It is known, for example, that the prion protein PrP performs a similar work in synapses, without which synaptic contacts weaken; and as for the precursor of beta-amyloid (Alzheimer's disease protein), it was found out that it is needed for the appearance and maturation of new neurons. Perhaps, by acting on such proteins in the right way, we will be able to reverse the destructive processes in the brain caused by mutant forms of these same proteins.
Portal "Eternal youth" http://vechnayamolodost.ru15.07.2014