The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age

The gamma phosphorylated form of the histone H2AX (gamma H2AX) was described more than 40 years ago and it was demonstrated that phosphorylation of H2AX was one of the first cellular responses to DNA damage. Since then, gamma H2AX has been implicated in diverse cellular functions in normal and pathological cells. In the first part of this review, we will briefly describe the intervention of H2AX in the DNA damage response (DDR) and its role in some pivotal cellular events, such as regulation of cell cycle checkpoints, genomic instability, cell growth, mitosis, embryogenesis, and apoptosis. Then, in the main part of this contribution, we will discuss the involvement of gamma H2AX in the normal and pathological central nervous system, with particular attention to the differences in the DDR between immature and mature neurons, and to the significance of H2AX phosphorylation in neurogenesis and neuronal cell death. The emerging picture is that H2AX is a pleiotropic molecule with an array of yet not fully understood functions in the brain, from embryonic life to old age.

Automated summary

The gamma phosphorylated form of histone H2AX, known as gamma H2AX, was discovered over 40 years ago and has been found to play a crucial role in the cellular response to DNA damage. It is involved in various cellular functions in both normal and pathological cells. Particularly, its involvement in the central nervous system, from immature to mature neurons, highlights its importance in neurogenesis and neuronal cell death, showcasing its pleiotropic nature with diverse functions from embryonic life to old age.