Necroptosis, Autophagy and Parthanatos in the Pathogenesis of Brain Diseases

Necroptosis, autophagy and parthanatos are three distinct but interrelated mechanisms of programmed cell death that significantly impact brain health and pathology and participate in both maintaining cellular homeostasis (by eliminating damaged or nonfunctional cells) and shaping neuroinflammatory responses. Dysregulations of these three processes are associated with a wide range of neurological and psychiatric disorders, from neurodegeneration (in Alzheimer’s and Parkinson’s diseases) to depression and schizophrenia. Here, we summarize clinical and preclinical data on the roles of necroptosis, autophagy and parthanatos in the pathogenesis of brain diseases, and discuss experimental models to study these forms of cell death and to test novel therapeutic approaches. A thorough understanding of molecular mechanisms underlying these processes opens opportunities for the development of drugs capable of simultaneously modulating several signaling pathways, thereby improving the prevention, diagnosis, and treatment of central nervous system disorders.