Huntington’s disease, the University of Trento discovers a new molecular aspect: “Research perspective to think about alternative methods to interfere with the disease”

Huntington’s disease, the University of Trento discovers a new molecular aspect: “Research perspective to think about alternative methods to interfere with the disease”
Huntington’s disease, the University of Trento discovers a new molecular aspect: “Research perspective to think about alternative methods to interfere with the disease”

TRENT. The molecular mechanisms of rare Huntington’s disease – hereditary, neurodegenerative and mainly affecting the nervous system – are very complex, and a group of researchers fromUniversity of Trento has discovered new information on the RNA molecule circular non-coding circHTT, which is a indicator of the alteration genetics responsible for the disease.

The study of the working group of Cibio Departmentpublished in the scientific journal Molecular Therapy Nucleic Acids, reveals a new molecular aspect of the disease – which in Italy cit affects seven thousand people, with forty thousand individuals at risk – with important functional implications on neurodegenerative mechanisms associated with the pathology.

There genetic cause of the disease of Huntington is to be attributed to mutationan expansion of a repeated stretch of DNA, which affects the HTT gene and the protein it produces, huntingtin: this condition initially causes the loss of nerve cells in specific areas of the brain, with the degeneration which then becomes more generalized, with the inevitable patient decline until death.

The research started in 2017 with the work of tesi by Alan Monzianione of the signatories of the publication, who first identified this molecule.

It was then Jasmin Morandel, first signatory of the article ed expert in the development of the nervous system central, to deepen the characterization of circHTT and to highlight the evolutionary and functional aspects of the molecule itself.

The important scientific result is result of integrated work and collaborative between Trentino research groups belonging to the Cibio Department and the Cnr, national, European and American.

“This is a particular study centered on an RNA molecule non-coding – explains the owner of the neuro epigenetics laboratory Marta Biagioli – that is, not responsible for the production of a certain protein, one of those molecules that until recently they were considered rubbish or rather junk RNA, because it was thought they were of no use”.

It’s thanks to the sequencing of the human genome that it was understood that only 3% of the genetic material codes for proteins, and most of the remaining 97%, however, is the so-called Non-coding DNA which is converted into Junk RNA, whose functions to date remain largely unknown.

“However in the last twenty years we began to understand that Junk RNA has important and useful functions – continues Biagioli – and the scientific world is deepening understanding of different classes of non-coding RNA, revealing them more and more clearly crucial functions biological”.

The RNA molecule characterized in the study – called as mentioned circHTT because it originates from the HTT gene implicated in Huntington’s disease – has a very stable circular structure and is found in high concentrations in the nervous system central of various mammals suggesting an important and conserved function, with researchers having discovered that this has a important role in disease.

“What we have seen is that every time there is‘expansion of the repeated sequence tract of the HTT gene, that is, in a pathological condition, there is a increased production of circHTT – comments the first signatory of the article Jasmin Morandell – and furthermore, by modifying the levels of circHTT, it is possible to intervene on some functional characteristics of the disease, the so-called phenotypes. This data offers us a new research perspective to be able to think of alternative methods to interfere with Huntington’s disease.”

 
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