Oxidative Stress, DNA Damage, and c-Abl Signaling: At the Crossroad in Neurodegenerative Diseases?

Figure 1

The figure illustrates the involvement of c-Abl in many cellular stress pathways. Oxidative stress, hyperglycemia, and DNA damage response induce c-Abl activation. In human neuroblastoma (SH-SY5Y cells), c-Abl targets p73, promoting neuronal death in response to hydrogen peroxide. In addition, c-Abl can also phophorylate Cdk5 and in tandem with Cdk5 can mediate p53 activation, promoting neuronal death. Hyperglycemia-induced apoptosis of NPCs is mediated by the translocation of the PKC𝛿-Abl complex to the nucleus. This translocation impacts on p53 activation leading to neuronal death. Oxidative DNA damage in Parkinson disorder is associated with increased c-Abl activity. c-Abl mediates tyrosine phosphorylation of Parkin and inhibits parkin’s ubiquitin E3 ligase activity.