Researchers show how to deal with different genetic diseases and neurodegenerative diseases – including Alzheimer’s and Parkinson’s – thanks to the mechanisms by which cells eliminate toxic molecules.
Clean equal health: a rule that applies to the cells. In a study published in the Journal of Cell Biology, Francesco Cecconi, a researcher at the Telethon Fondazione IRCCS Saint Lucia and the University of Rome Tor Vergata, clarified new and important aspects of the mechanisms by which cells to clean up toxic molecules. The discovery not only provides important information about a mechanism widely conserved in nature, that autophagy, but also suggests new potential drug targets. The “clean cell” was indeed a very important role in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, but also in genetic diseases such as lysosomal storage disease, Huntington’s and muscular dystrophy, and in many forms of tumor. Disorders are very different, but united by the fact that damaged cellular materials accumulate gradually damaging the tissues. Able to regulate the pharmacological processes of autophagy could prove the winning move to protect cells and improve symptoms in patients.
The mechanism of autophagy – or autodigestion – is already known from the sixties, but there is still much to discover about the various molecules involved and their role.
In the process of disposing of waste, the substances to be eliminated (mutant proteins, damaged mitochondria and other waste materials) are incorporated into vesicles called autophagosomes. The content is then transported and released in lysosomes, cell organelles involved in the degradation itself.
The team of Francesco Cecconi, in collaboration with other researchers at the Lazzaro Spallanzani in Rome, considered a protein called dynein, which drives the movement of material along microtubules, a sort of “rails” inside the cell. The researchers found that the regulation of this motor is due to their old acquaintance: the protein AMBRA1, discovered from them in 2007, known to be a crucial factor nell’autofagia. Mutations in the gene AMBRA1 fact lead to a lack of development of the nervous system and embryonic death. In particular, the study just published shows that dynein is linked directly to AMBRA1 AMBRA1 and that when the link melts, it starts the transport of vesicles to the site of autophagosome degradation. The bond rupture is mediated by the action of another protein kinase ULK1.
“In the future we plan to develop small molecules,” says Cecconi, “able to interact with and AMBRA1 ULK1, so as to modulate the mechanisms of autophagy in a” sweet “. There are already drugs that induce it, but they do so too exuberant, and then harm the cells. ” In doing so, the fine tuning of autophagy may be a therapeutic strategy against neurodegeneration without side effects. “Ours is a basic research,” concludes the researcher, “but hopefully this time of great application prospect.”
