Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme involved in the base excision repair (BER) pathway, which repairs oxidative base damage caused by endogenous and exogenous agents. APE1 acts as a reductive activator of many transcription factors (TFs) and has also been named redox effector factor 1, Ref-1. For example, APE1 activates activator protein-1, nuclear factor kappa B, hypoxia-inducible factor 1alpha, paired box gene 8, signal transducer activator of transcription 3 and p53, which are involved in apoptosis, inflammation, angiogenesis and survival pathways. APE1/Ref-1 maintains cellular homeostasis (redox) via the activation of TFs that regulate various physiological processes and that crosstalk with redox balancing agents (for example, thioredoxin, catalase and superoxide dismutase) by controlling levels of reactive oxygen and nitrogen species. The efficiency of APE1/Ref-1's function(s) depends on pairwise interaction with participant protein(s), the functions regulated by APE1/Ref-1 include the BER pathway, TFs, energy metabolism, cytoskeletal elements and stress-dependent responses. Thus, APE1/Ref-1 acts as a 'hub-protein' that controls pathways that are important for cell survival. In this review, we will discuss APE1/Ref-1's versatile nature in various human etiologies, including neurodegeneration, cancer, cardiovascular and other diseases that have been linked with alterations in the expression, subcellular localization and activities of APE/Ref-1. APE1/Ref-1 can be targeted for therapeutic intervention using natural plant products that modulate the expression and functions of APE1/Ref-1. In addition, studies focusing on translational applications based on APE1/Ref-1-mediated therapeutic interventions are discussed.
Animals ; DNA Damage ; DNA Repair ; DNA-(Apurinic or Apyrimidinic Site) Lyase/analysis/genetics/*metabolism ; Humans ; *Molecular Targeted Therapy/methods ; Neoplasms/*drug therapy/genetics/*metabolism ; Neurodegenerative Diseases/*drug therapy/genetics/*metabolism ; Oxidative Stress ; Phytochemicals/pharmacology/*therapeutic use ; Polymorphism, Genetic ; Protein Interaction Maps

STUDY DESIGN: Prospective clinical study. PURPOSE: To observe the usefulness of anterior cervical osteophytes as intrinsic markers for spinal level localization (SLL) during sub-axial cervical spinal surgery via the anterior approach. OVERVIEW OF LITERATURE: Various landmarks, such as the mandibular angle, hyoid bone, thyroid cartilage, first cricoid ring, and C6 carotid tubercle, are used for gross cervical SLL; however, none are used during cervical spinal surgery via the anterior approach. We present our preliminary assessment of SLL over anterior vertebral surfaces (i.e., intrinsic markers) in 48 consecutive cases of anterior cervical spinal surgeries for the disc-osteophyte complex (DOC) in degenerative diseases and granulation or tumor tissue associated with infectious or neoplastic diseases, respectively, at an ill-equipped center. METHODS: This prospective study on patients undergoing anterior cervical surgery for various sub-axial cervical spinal pathologies aimed to evaluate the feasibility and accuracy of SLL via intraoperative palpation of disease-related morphological changes on anterior vertebral surfaces visible on preoperative midline sagittal T1/2-weighted magnetic resonance images. RESULTS: During a 3-year period, 48 patients (38 males,10 females; average age, 43.58 years) who underwent surgery via the anterior approach for various sub-axial cervical spinal pathologies, including degenerative disease (n= 42), tubercular infection (Pott's disease; n=3), traumatic prolapsed disc (n=2), and a metastatic lesion from thyroid carcinoma (n=1), comprised the study group. Intrinsic marker palpation yielded accurate SLL in 79% of patients (n=38). Among those with degenerative diseases (n=42), intrinsic marker palpation yielded accurate SLL in 76% of patients (n=32). CONCLUSIONS: Intrinsic marker palpation is an attractive potential adjunct for SLL during cervical spinal surgeries via the anterior approach in well-selected patients at ill-equipped centers (e.g., those found in developing countries). This technique may prove helpful when radiographic visualization is occasionally inadequate.
Clinical Study ; Female ; Humans ; Hyoid Bone ; Intervertebral Disc Displacement ; Osteophyte ; Palpation ; Pathology ; Prospective Studies ; Spine* ; Spondylosis ; Thyroid Cartilage ; Thyroid Neoplasms