5‐LOX: blood based biomarker for Alzheimer’s disease (AD) and effect of peptide inhibitor on neurotoxicity developed in AD.

Abstract

AbstractBackgroundThe inflammatory process plays a key role in neurodegenerative disorder. Pro‐inflammatory molecule, 5‐Lipooxygenase (5‐LOX), protein is involved in pathologic phenotype of AD. It includes Aβ amyloid deposition and tau hyper phosphorylation both but the detail mechanism is still illusive. This study determined the level of 5‐LOX in serum of Alzheimer’s disease (AD) patient, Mild cognitive impairment (MCI), normal elderly and rescue effect by YWCS, a peptide inhibitor of 5‐LOX on neurotoxicity by Aβ amyloid (Aβ25‐35) in neuroblastoma cells SH‐SY5Y.MethodThe level of serum 5‐LOX was estimated by surface plasmon resonance and presence of 5‐LOX in serum was confirmed by western blot. The peptide inhibitor YWCS was synthesized by solid‐phase peptide synthesis (SPPS) using F‐moc and Wang resin chemistry, and the purity of the peptide was verified by analytical RP‐HPLC. The neuroprotective effect of 5‐LOX peptide inhibitor YWCS in Aβ25‐35 induced neurotoxicity was analyzed by MTT assay and western blotting.ResultThe level of serum 5‐LOX was estimated by surface plasmon resonance and presence of 5‐LOX in serum was confirmed by western blot. The peptide inhibitor YWCS was synthesized by solid‐phase peptide synthesis (SPPS) using F‐moc and Wang resin chemistry, and the purity of the peptide was verified by analytical RP‐HPLC. The neuroprotective effect of 5‐LOX peptide inhibitor YWCS in Aβ25‐35 induced neurotoxicity was analyzed by MTT assay and western blotting.ConclusionThe differential expression of serum 5‐LOX among the study groups suggests, it can be one of potential serum protein marker and therapeutic regimen for AD and MCI. Peptide YWCS, can serve as new platform as 5‐LOX inhibitor which can prevent neurotoxicity developed in AD.