Abstract <p>Necroptosis, autophagy and parthanatos are three distinctbut interrelated mechanisms of programmed cell death that significantlyimpact brain health and pathology and participate in both maintainingcellular homeostasis (by eliminating damaged or nonfunctional cells)and shaping neuroinflammatory responses. Dysregulations of thesethree processes are associated with a wide range of neurologicaland psychiatric disorders, from neurodegeneration (in Alzheimer’sand 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 deathand to test novel therapeutic approaches. A thorough understandingof molecular mechanisms underlying these processes opens opportunitiesfor the development of drugs capable of simultaneously modulatingseveral signaling pathways, thereby improving the prevention, diagnosis,and treatment of central nervous system disorders.</p>