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Autophagy Activation Alleviates Amyloid-β-Induced Oxidative Stress, Apoptosis and Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells

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Abstract

Autophagy is an evolutionary conserved catabolic process that ensures continuous removal of damaged cell organelles and long-lived protein aggregates to maintain cellular homeostasis. Although autophagy has been implicated in amyloid-β (Aβ) production and deposition, its role in pathogenesis of Alzheimer’s disease remains elusive. Thus, the present study was undertaken to assess the cytoprotective and neuroprotective potential of autophagy on Aβ-induced oxidative stress, apoptosis and neurotoxicity in human neuroblastoma SH-SY5Y cells. The treatment of Aβ1-42 impaired the cell growth and redox balance, and induced apoptosis and neurotoxicity in SH-SY5Y cells. Next, the treatment of rapamycin (RAP) significantly elevated the expression of autophagy markers such as microtubule-associated protein-1 light chain-3 (LC3), sequestosome-1/p62, Beclin-1, and unc-51-like kinase-1 (ULK1) in SH-SY5Y cells. RAP-induced activation of autophagy notably alleviated the Aβ1-42-induced impairment of redox balance by decreasing the levels of pro-oxidants such as reactive oxygen species, lipid peroxidation and Ca2+ influx, and concurrently increasing the levels of antioxidant enzymes such as superoxide dismutase and catalase. The RAP-induced autophagy also ameliorated Aβ1-42-induced loss of mitochondrial membrane potential and apoptosis. Additionally, the activated autophagy provided significant neuroprotection against Aβ1-42-induced neurotoxicity by elevating the expression of neuronal markers such as synapsin-I, PSD95, NCAM, and CREB. However, 3-methyladenine treatment significantly exacerbated the neurotoxic effects of Aβ1-42. Taken together, our study demonstrated that the activation of autophagy provided possible neuroprotection against Aβ-induced cytotoxicity, oxidative stress, apoptosis, and neurotoxicity in SH-SY5Y neuronal cells.

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Acknowledgements

Dr. D. S. Kotahri Post Doctoral Fellowship scheme of University Grants Commission, New Delhi, India, is acknowledged for providing financial support (F.4-2/2006(BSR)/BL/14-15/0326) and fellowship to A. K. Singh.

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  1. Department of Biochemistry, University of Allahabad, Allahabad, 211002, India

    Abhishek Kumar Singh & Syed Ibrahim Rizvi

  2. Department of Biomedical Engineering, National Institute of Technology, Raipur, 492010, India

    Akalabya Bissoyi

  3. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Mahendra Pratap Kashyap

  4. Department of Biochemistry, Pt. JNM Medical College, Raipur, 492001, India

    Pradeep Kumar Patra

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  1. Abhishek Kumar Singh
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Correspondence to Abhishek Kumar Singh.

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Singh, A.K., Bissoyi, A., Kashyap, M.P. et al. Autophagy Activation Alleviates Amyloid-β-Induced Oxidative Stress, Apoptosis and Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells. Neurotox Res 32, 351–361 (2017). https://doi.org/10.1007/s12640-017-9746-5

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