A protein with a double duty against neurodegeneration

The unexpected double job of a crucial protein for cells, called DDX11 , has been discovered: in addition to playing the role of mechanic in the cell nucleus, where it opens the double helix of DNA to allow replication and repair , it also works as a scavenger in the cytoplasm to regulate waste recycling . This is indicated by the study conducted by the Institute of Biochemistry and Cellular Biology of the National Research Council in collaboration with the University of Naples Federico II. The results, published in the journal Autophagy, open the way to new strategies against rare genetic and neurodegenerative diseases such as Parkinson's and Alzheimer's . The DDX11 protein had already been known for some time for its function as a DNA helicase , which sees it operate in the nucleus of cells to separate the two strands of the double helix and thus allow the intervention of the proteins that deal with replication and repair . Researchers have now discovered that it is also active in the cytoplasm of cells, where it is involved in the regulation of autophagy , the process by which damaged and no longer functioning organelles and proteins are recycled . "We observed that, in the absence of DDX11 , cells lose the ability to correctly form autophagosomes , the 'shuttles' that transport cellular waste to lysosomes for degradation: this compromises the removal of toxic aggregates", observes Raffaella Bonavita, first author of the study. Another key element that emerged from the study concerns the interaction between DDX11 and the protein p62/SQSTM1 , a fundamental receptor for selecting and loading deteriorated proteins and organelles into autophagosomes. Autophagy is now considered an essential mechanism for the health of the nervous system and its alteration has been linked to numerous neurodegenerative diseases , including Parkinson's , Alzheimer's , ALS and ataxia with oculomotor apraxia type 2. The direct involvement of DDX11 in this process opens up completely new perspectives , both for rare genetic diseases such as Warsaw Breakage Syndrome , which compromises physical and neurological development, and for neurodegenerative diseases .