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5-LOX in Alzheimer’s Disease: Potential Serum Marker and In Vitro Evidences for Rescue of Neurotoxicity by Its Inhibitor YWCS

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Abstract

The inflammatory process plays a key role in neurodegenerative disorder. The inflammatory molecule, 5-lipooxygenase (5-LOX), protein is involved in the pathologic phenotype of Alzheimer’s disease (AD) which includes Aβ amyloid deposition and tau hyperphosphorylation. This study determined the level of 5-LOX in serum of AD patients, mild cognitive impairment (MCI) patients, and the normal elderly, and the rescue effect by YWCS, a peptide inhibitor of 5-LOX on neurotoxicity by Aβ amyloid25–35 (Aβ25–35) in neuroblastoma cells. The concentration of serum 5-LOX was estimated by surface plasmon resonance and western blot. The neuroprotective effect of 5-LOX peptide inhibitor YWCS in Aβ25–35-induced neurotoxicity was analyzed by MTT assay and western blotting. We found significant upregulated serum 5-LOX in AD patients and also in MCI patients compared to the normal control group. The peptide inhibitor of 5-LOX, YWCS, prevented the neurotoxic effect of Aβ25–35 by reducing the expression of γ-secretase as well as p-Tau181 in SH-SY5Y cells. However, YWCS was nontoxic towards normal HEK cells. The differential expression of serum 5-LOX among the study groups suggests it can be one of potential serum protein marker and a therapeutic regimen for AD and MCI. The negative correlation with neuropsychological parameters, i.e., MoCA and HMSE, increases its importance and makes it useful during the clinical setup which is very needful in developing countries. Peptide YWCS can serve as a new platform as a 5-LOX inhibitor which can prevent neurotoxicity developed in AD.

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Acknowledgements

The authors acknowledge the Research Section, All India Institute of Medical Sciences, for providing the intramural grant and funds for the consumable items and DST, government of India, for the fellowship of Nitish Rai.

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Authors and Affiliations

  1. Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Shashank Shekhar, Nitish Rai, Rahul Kumar, Yudhishthir Yadav & Sharmistha Dey

  2. Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India

    Saroj Kumar Yadav & Aparajit B. Dey

  3. Department of Neurology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Manjari Tripathi

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  1. Shashank Shekhar
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  2. Saroj Kumar Yadav
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  4. Rahul Kumar
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  5. Yudhishthir Yadav
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Correspondence to Sharmistha Dey.

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The Ethics Committee of AIIMS approved the study protocol (IESC/T-439/23.12.2014). Informed consent in writing was obtained from the controls, patients, or their attendants (if a patient is incapable of making a signature). The study was carried out as per the guidelines of the Ethics Committee.

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Shekhar, S., Yadav, S.K., Rai, N. et al. 5-LOX in Alzheimer’s Disease: Potential Serum Marker and In Vitro Evidences for Rescue of Neurotoxicity by Its Inhibitor YWCS. Mol Neurobiol 55, 2754–2762 (2018). https://doi.org/10.1007/s12035-017-0527-1

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  • DOI: https://doi.org/10.1007/s12035-017-0527-1

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