Figure 5

Apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor-1 (Ref-1) has a pivotal role in various human diseases. Owing to its vital role in the BER pathway, in balancing intra-cellular redox states and in the reductive activation of various transcription factors (TFs) controlling cell survival pathways, alterations in APE1/Ref-1 expression and functions have a crucial role in various human diseases including cancer, cardiovascular disease (CVD) and neurodegenerative diseases (NDs). The overexpression and enhanced enzymatic activities of APE1/Ref-1 have been linked with the conferral of survival advantage and chemoresistance in cancer cells. APE1/Ref-1 also has an important role in CVD by governing H-Ras-mediated endothelial nitric oxide synthase (eNOS) activity and NO bioavailability. In NDs, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotropic lateral sclerosis (ALS), decreased neuronal expression of APE1/Ref-1 after neuronal insult decreases cell viability and promotes neurodegeneration. In addition to alterations in the expression of APE1/Ref-1 and its subcellular localization and enzymatic functions, single-nucleotide polymorphisms (SNPs) in the APE1/Ref-1 gene have been also reported to have a role in ALS, AD and cancer. In addition, various post-translational modifications (PTMs), such as acetylation,⁷ ubiquitination,^{93, 100} s-nitrosylation,²³⁴ sumoylation²¹ and phosphorylation,²³⁵ have been demonstrated to regulate APE1/Ref-1 functions in various human diseases.