What would happen if no one in your city took care of removing the garbage we generate and the damaged objects? Probably that over time your town would collapse. On the contrary, when we collect waste, it is processed, recycled and reused to manufacture other materials. Well, this also happens in our body. On a regular basis, cells generate waste products and other altered cellular contents that we are able to eliminate and reuse for the production of new essential elements for the cell. This process that our cells carry out and that enables their survival is known as autophagy – literally “eating itself” in Greek – and it was called that for the first time in 1963 by the Belgian biochemist Christian de Duve, Nobel Prize in Physiology or Medicine.
The importance of this biochemical process for the normal development of cell physiology has spread interest in its study over the last decades. In this sense, the contributions of Daniel Klionsky in Ann Harbor, of Guido Kroemer in Paris or of the Spanish Ana Cuervo in New York stand out. However, autophagy not only participates in the proper functioning of our body, but also acts against an aggressive stimulus or a cellular defect . In this way, the cell goes into autophagy to repair the damage. That is why the involvement of this mechanism can lead to the development or worsening of different disorders such as Huntington’s disease, Alzheimer’s and Parkinson’s, all of them neurodegenerative pathologies.
Autophagy and Parkinson’s disease
And what do these diseases have in common? Well, all of them present an intra or extracellular accumulation of altered or misfolded proteins, which we must eliminate and recycle precisely through autophagy. And if this process is affected, the cell is not able to carry out the cleaning of these residues . Thus, in Parkinson’s disease, accumulations of incorrectly eliminated proteins occur, among which synuclein stands out. This protein is important because it is involved in the formation of Lewy bodies in the brain, one of the most characteristic pathological features of the disease.
Although Parkinson’s is a disease that is due to many causes, experts agree that environmental and genetic factors converge at its origin, and it is curious that many of the latter produce molecular tools that either participate in the autophagy process, or regulate or modify it. One of them, known as LRRK2 or dardarina – derived from the Basque word dardara which means tremor – is closely related to the disease. In recent years, our PARK research group has studied cells from Parkinson’s patients that present one of the most prevalent mutations in the enzyme dardarin. In this way, we have verified that the autophagy mechanism is substantially modified in these cells, and that this modulation makes the cells more sensitive to some of the environmental factors related to the disease . Thus, in the same model we find both groups of predisposing factors, the environmental and the genetic. Such research is available in scientific journals such as Autophagy .
Autophagy, therefore, is becoming a new strategy in the fight against neurodegenerative diseases and to prolong the life of cells , accelerating or delaying this cleaning process, although this probably deserves another chapter.
José Manuel Fuentes Rodríguez is a researcher at the Department of Biochemistry and Molecular Biology and Genetics at the University of Extremadura and Principal Investigator of the PARK group, integrated into the Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) of the Health Institute III (ISCIII) . This article has been written in collaboration with the UEx Scientific Culture Diffusion Service.
Image: Cell from a Parkinson’s patient showing an alteration in autophagy, evidenced by the accumulation of a red-marked protein. University of Extremadura.
