Neuronal cell death: an overview of its different forms in central and peripheral neurons

The discovery of neuronal cell death dates back to the nineteenth century. Nowadays, after a very long period of conceptual difficulties, the notion that cell death is a phenomenon occurring during the entire life course of the nervous system, from neurogenesis to adulthood and senescence, is fully established. The dichotomy between apoptosis, as the prototype of programmed cell death (PCD ), and necrosis, as the prototype of death caused by an external insult, must be carefully reconsidered, as different types of PCD: apoptosis, autophagy, pyroptosis, and oncosis have all been demonstrated in neurons (and glia ). These modes of PCD may be triggered by different stimuli, but share some intracellular pathways such that different types of cell death may affect the same population of neurons according to several intrinsic and extrinsic factors. Therefore, a mixed morphology is often observed also depending on degrees of differentiation, activity, and injury. The main histological and ultrastructural features of the different types of cell death in neurons are described and related to the cellular pathways that are specifically activated in any of these types of PCD.