Neuroprotective Effect of NO-Delivery Dinitrosyl Iron Complexes (DNICs) on Amyloid Pathology in the Alzheimer’s Disease Cell Model

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment, memory loss, and behavioral deficits. β-amyloid_1-42 (Aβ_1-42) aggregation is a significant cause of the pathogenesis in AD. Despite the numerous types of research, the current treatment efficacy remains insufficient. Hence, a novel therapeutic strategy is required. Nitric oxide (NO) is a multifunctional gaseous molecule. NO displays a neuroprotective role in the central nervous system by inhibiting the Aβ aggregation and rescuing memory and learning deficit through the NO signaling pathway. Targeting the NO pathway might be a therapeutic option; however, NO has a limited half-life under the biological system. To address this issue, a biomimetic dinitrosyl iron complex [(NO)₂Fe(μ-SCH₂CH₂COOH)₂Fe(NO)₂] (<b>DNIC-COOH</b>) that could stably deliver NO was explored in the current study. To determine whether <b>DNIC-COOH</b> exerts anti-AD efficacy, <b>DNIC-COOH</b> was added to neuron-like cells and primary cortical neurons along with Aβ_1-42. This study found that <b>DNIC-COOH</b> protected neuronal cells from Aβ-induced cytotoxicity, potentiated neuronal functions, and facilitated Aβ_1-42 degradation through the NO-sGC-cGMP-AKT-GSK3β-CREB/MMP-9 pathway.