5-LOX in Alzheimer’s Disease: Potential Serum Marker and In Vitro Evidences for Rescue of Neurotoxicity by Its Inhibitor YWCS
| Autor: | Rajesh Kumar, Aparajit Ballav Dey, Shashank Shekhar, Yudhishthir Yadav, Saroj Kumar Yadav, Sharmistha Dey, N. Rai, Manjari Tripathi |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Neurotoxicity Syndrome Cell Survival Neuroscience (miscellaneous) tau Proteins Pharmacology Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Western blot Alzheimer Disease Cell Line Tumor medicine Humans Lipoxygenase Inhibitors Phosphorylation Aged Arachidonate 5-Lipoxygenase biology medicine.diagnostic_test business.industry HEK 293 cells Neurotoxicity food and beverages medicine.disease Blot HEK293 Cells 030104 developmental biology ROC Curve Neurology Case-Control Studies Immunology biology.protein Female Neurotoxicity Syndromes Amyloid Precursor Protein Secretases Alzheimer's disease Peptides business Amyloid precursor protein secretase Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Molecular Neurobiology. 55:2754-2762 |
| ISSN: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-017-0527-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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