Ataxia-Telangiectasia mutated plays an important role in cerebellar integrity and functionality

Abstract

Accumulating evidence indicates that ataxia-Telangiectasia mutated kinase is critical for maintaining cellular homeostasis and that it has both nuclear and cytoplasmic functions. However, the functions of ataxia-Telangiectasia mutated that when lost lead to cerebellar degeneration are still unknown. In this review, we first describe the role of ataxia-Telangiectasia mutated in cerebellar pathology. In addition to its canonical nuclear functions in DNA damage response circuits, ataxia-Telangiectasia mutated functions in various cytoplasmic and mitochondrial processes that are critically important for cellular homeostasis. We discuss these functions with a focus on the role of ataxia-Telangiectasia mutated in maintaining the homeostatic redox state. Finally, we describe the unique functions of ataxia-Telangiectasia mutated in various types of neuronal and glial cells including cerebellar granule neurons, astrocytes, and microglial cells.