School Of Basic And Applied Sciences
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Item Effect of amyloid beta (25-35) peptide on mitochondrial respiratiory function in neuroral cells over expressing ape1(Central University of Punjab, 2014) Kaur, Navrattam; Mantha, Anil K.Alzheimer's disease (AD) is an important public health problem which affects millions of people worldwide. The major pathological hallmarks associated with AD are the accumulation of amyloid beta (A?) in senile plaques and neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau proteins. Accumulating evidences point towards the role of oxidative stress and mitochondrial dysfunction in the pathogenesis of AD. Aging is considered as one of the greatest risk factor for AD. In order to maintain genome integrity, base excision repair (BER) pathway is the predominant pathway for repairing oxidized base lesions in neuronal cells. APE1 is the central enzyme of the BER-pathway, having both repair and redox activities and shown to enhance neuronal survival after oxidative stress. In my study, effect of A?(25-35) on mitochondrial ROS/RNS levels and activities of respiratory complexes (I, III, & IV) in neuronal cells was studied with and without ectopic APE1 expression and the neuro- modulatory role of Ginkgolide B (from leaves of G. biloba) was evaluated. It was seen that A?(25-35) increases the ROS/RNS levels in these cells which was decreased when pre-treated with Ginkgolide B (G.B) before treating with A?(25-35). APE1 levels were found to be decreased on treating with A?(25-35) and were increased on pre- treatment with G.B and subsequent treatment with A?(25-35). These results indicate that ectopic APE1 expression in the mitochondria of the neuronal cells might overcome the oxidative damage caused by A?(25-35). Also, phytochemical G.B has shown to modulate the mitochondrial complex activity upon A?(25-35)-induced oxidative stress and modulate the ROS/RNS levels in the presence of APE1. Further studies are needed to understand the mechanism of action of APE1 in relation to the above results, which will be carried out during my Ph.D. work.Item A review on protein–protein interaction network of APE1/Ref-1 and its associated biological functions(Wiley, 2015) Thakur, S.; Dhiman, Monisha; Tell, G.; Mantha, Anil K.Apurinic/apyrimidinic endonuclease 1 (APE1) is a classic example of functionally variable protein. Besides its well-known role in (i) DNA repair of oxidative base damage, APE1 also plays a critical role in (ii) redox regulation of transcription factors controlling gene expression for cell survival pathways, for which it is also known as redox effector factor 1 (Ref-1), and recent evidences advocates for (iii) coordinated control of other non-canonical protein–protein interaction(s) responsible for significant biological functions in mammalian cells. The diverse functions of APE1 can be ascribed to its ability to interact with different protein partners, owing to the attainment of unfolded domains during evolution. Association of dysregulation of APE1 with various human pathologies, such as cancer, cardiovascular diseases and neurodegeneration, is attributable to its multifunctional nature, and this makes APE1 a potential therapeutic target. This review covers the important aspects of APE1 in terms of its significant protein–protein interaction(s), and this knowledge is required to understand the onset and development of human pathologies and to design or improve the strategies to target such interactions for treatment and management of various human diseases. Copyright © 2015 John Wiley & Sons, Ltd.