Neurology Central

The role of epigenomics in the neurodegeneration of ataxia-telangiectasia

0

Ataxia-telangiectasia (A-T) is a multisystem disease characterized by neurodegeneration in the CNS [1–5]. The earliest and most profound neuropathology involves the Purkinje and granule cells of the cerebellum. A-T is caused by mutation of the A-T mutated (ATM) gene, which is ubiquitously expressed throughout development and encodes a serine/threonine protein kinase of the phosphatidylinositol-3 kinase-related kinase family [6]. A-T is classified as a rare neurodegenerative disease, mainly impacting on cerebellum integrity and functioning, resulting in a progressive deterioration of motor functional capabilities [5]. Moreover, since there is currently no effective treatment to cure or even slow down the rate of cerebellar neurodegeneration, A-T significantly decreases life quality of those suffering from it. The best-known function of ATM is to ensure the integrity of the genome. After DNA damage, ATM activates cell cycle checkpoints, arresting the cycle until DNA repair is complete [7]. Its role in maintaining the health and survival of neurons is complex. Consistent with its function in DNA damage repair [8], ATM protects postmitotic neurons from degeneration by suppressing the cell cycle [9–11]. While non-neurological phenotypes are also found, including immune system defects, germ cell defects, hypersensitivity to ionizing radiation and increased susceptibility to, it is the origins of the CNS motor phenotypes of A-T that are the most poorly understood. Yet the pathway that leads from these defects to neuronal cell loss and the other classical neurological phenotypes remains unknown.

Click here to view full article [/userpro_private]

Share:

Leave A Comment