A new mechanism underpinning ALS has been discovered
The ubiquitin ligase enzyme Hecw seems essential for maintaining the integrity of neurons, which SLA destroys, and could be useful for developing specific drugs
(photo: KTSDESIGN / Science Photo Library / Getty Images) I Ifom and University of Milan researchers have taken a step forward towards understanding the mechanisms that cause amyotrophic lateral sclerosis (ALS), a rare but very serious neurodegenerative disease that affects about a thousand people every year in Italy. An enzyme, called ubiquitin ligase Hecw, would be essential to maintain the integrity of neurons. The study was published in the journal Nature Communications.Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis, or ALS, affects 2 in 100,000 people worldwide every year. In Italy the annual number of new diagnoses is about one thousand. ALS is a very disabling neurodegenerative disease, which generally takes away the ability to move, speak, and then the ability to swallow and breathe alone within a few years, while leaving the conscience intact. To date, there is no cure or therapy capable of slowing down its progression. Also because it is considered a multifactorial disease, the causes of which are still little known.An enzyme for the integrity of neurons
This is why every new discovery on the biological mechanisms of neurons is so significant. . Discoveries such as the one - unpublished - made by the Milanese researchers of Ifom and the Milanese State University, who in Nature Communications explain how the enzyme called ubiquitin ligase Hecw is essential to maintain the integrity of neurons, so that they develop and function in a correct.For neurons to be intact, perfect spatio-temporal coordination is required, which means that certain proteins in the cell only need to be produced at a specific time and place.
" This coordination takes place thanks to the packaging of their messenger Rna (mRna) in protein organelles called Rnp (ribonucleoproteins) ", explains Simona Polo, head of the Ifom molecular complexes and signal transmission laboratory and lecturer at the Oncology and Hemato-Oncology Department at the 'University of Milan. And she adds: "Protein factors exercise a very strict control over mRna, preventing it from being translated into proteins until it reaches its destination. If this control is lacking, for example due to mutations in some of these factors, neuronal integrity is compromised and the onset of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (Ftd) is promoted. Knowing the regulation mechanism is therefore an essential step towards the cure ”.
The study, carried out with an innovative approach of combining biophysical and animal models (Drosophila melanogaster or fruit fly), has allowed us to understand that the ubiquitin protein is attached to the Rnp by the ubiquitin ligase enzyme Hecw, modifying them and preventing mRna from being converted into proteins. Without the enzyme, therefore without ubiquitin, the Rnp from liquid granules ("which separate in the cell like a drop of oil in water", explains Valentina Fajner who conducted the experiments) become gelatinous: their function is compromised and the mRna regulation fails. Neurons are damaged and die.
"Having identified an enzyme, the ubiquitin ligase Hecw, which specifically regulates a process underlying neurodegenerative diseases such as ALS, represents a further step that the research adds in the path towards their treatment and this is particularly important in a field such as that of neurodegenerative diseases, in which there is a great lack of resolutive therapeutic interventions ", concludes Polo:" Understanding the factors involved in the development of diseases offers new targets for development of specific drugs. Furthermore, we now know that also for these pathologies the timeliness of intervention is very important: identifying factors that, if changed, can lead to the development of diseases is fundamental to have new references for early diagnosis ".
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Neurodegenerative diseases Health globalData.fldTopic = "Neurodegenerative diseases, Health"
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