American researchers have identified a hitherto unknown mechanism involved in cases of microcephaly. These discoveries could potentially open the way to avenues of treatment, but also help to better understand the process of formation of certain cancers.
- Microcephaly, an abnormally small size of the skull, is a congenital malformation
- Gene therapy could help restore brain growth
Microcephaly refers to a congenital malformation characterized by an abnormally small size of the skull. The number of new cases of microcephaly worldwide has increased significantly since the appearance of the Zika virus in Latin America in 2015 and represents a real public health challenge. Microcephaly can indeed have many consequences on the mental development of the child: learning difficulties, loss of vision and hearing, movement disorders, etc.
In an attempt to better understand the mechanisms involved in the onset of microcephaly, American researchers from the University of Virginia (UVA) School of Medicine studied the functioning of the final stage of cell division, called “abscission ” and during which a “daughter” cell, which cuts its link with its “mother” cell. For this rupture to take place correctly, the presence of a particular cellular protein, called Cep55, is required.
Greater “quality control” in brain cells
“By understanding the genetic causes of microcephaly, although rare, we can also help understand how certain viral infections can cause microcephaly, such as Zika virus or cytomegalovirus“, underlines Noelle D. Dwyer, PhD, researcher in the cell biology department of the UVA and co-author of the study, published in The Journal of Neuroscience.
The research team carried out laboratory tests to try to understand what would happen to the brain in the absence of the Cep55 protein. Experiments performed on laboratory mice showed that abscission could still occur in rodents in the absence of the protein, but with a longer than usual process and a higher failure rate.
When abscission fails, extensive neural stem cell death occurs. The damaged brain cells will kind of sacrifice themselves,”to prevent abnormal brain cells from causing brain dysfunction or brain tumors“, explains Noelle D. Dwyer. This process, described as “quality control”, is not as strict in other organs of the body, the researchers note.
A discovery that could also help understand cancer
Blocking the cell death signal with drugs or gene therapy might help restore brain growth in some types of microcephaly, but it might also worsen brain function, according to the study. Hence the importance of continuing to experiment with these treatment options in animal or cell culture models, the scientists stress.
If these findings confirm what science has already established regarding the gene associated with the production of the Cep55 protein, they explain why people with mutations in the Cep55 gene suffer from severe brain and central nervous system deficiencies, whereas the rest of their body is relatively spared.
New elements that could also prove useful in the fight against cancer. “Mutations in the Cep55 gene are also associated with many human cancers, so understanding the normal function of the Cep55 gene in dividing cells in the brain helps inform cancer researchers about how its altered function could lead to abnormal cell division that could initiate or fuel tumor growth“, says Noelle D. Dwyer.
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