On the role of autophagy in human diseases: a gender perspective

Cytopathological features of cells from males and females, i.e. XX and XY isolated cells, have been demonstrated to represent a key variable in the mechanism underlying gender disparity in human diseases. Major insights came from the studies of gender differences in cell fate, e.g. in apoptotic susceptibility. We report here some novel insights recently emerged from literature that are referred as to a cytoprotection mechanism by which cells recycle cytoplasm and dispose of excess or defective organelles, i.e. autophagy. Autophagy and related genes have first been identified in yeast. Orthologue genes have subsequently been found in other organisms, including human beings. This stimulated the research in the field and, thanks to the use of molecular genetics and cell biology in different model systems, autophagy gained the attention of several research groups operating to analyse the pathogenetic mechanisms of human diseases. It remains unclear, however, whether autophagy can exert a protective effect or instead contribute to the pathogenesis of important human diseases. On the basis of the growing importance of sex/gender as key determinant of human pathology and of the known differences between males and females in the onset, progression, drug susceptibility and outcome of a plethora of diseases, the idea that autophagy could represent key and critical factor should be taken into account. In the review, we summarize our current knowledge about the role of autophagy in some paradigmatic human diseases (cancer, neurodegenerative, autoimmune, cardiovascular) and the role of ‘cell sex’ differences in this context.