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

Alzheimer's disease (AD) isa neurodegenerative disordercharacterized by cognitive impairment, memory loss, and behavioraldeficits. & beta;-amyloid(1-42) (A & beta;(1-42)) aggregation is a significant cause of the pathogenesis in AD. Despitethe numerous types of research, the current treatment efficacy remainsinsufficient. Hence, a novel therapeutic strategy is required. Nitricoxide (NO) is a multifunctional gaseous molecule. NO displays a neuroprotectiverole in the central nervous system by inhibiting the A & beta; aggregationand rescuing memory and learning deficit through the NO signalingpathway. Targeting the NO pathway might be a therapeutic option; however,NO has a limited half-life under the biological system. To addressthis issue, a biomimetic dinitrosyl iron complex [(NO)(2)Fe(& mu;-SCH2CH2COOH)(2)Fe(NO)(2)] (DNIC-COOH) that could stably deliver NO wasexplored in the current study. To determine whether DNIC-COOH exerts anti-AD efficacy, DNIC-COOH was added to neuron-likecells and primary cortical neurons along with A & beta;(1-42). This study found that DNIC-COOH protected neuronalcells from A & beta;-induced cytotoxicity, potentiated neuronal functions,and facilitated A & beta;(1-42) degradation throughthe NO-sGC-cGMP-AKT-GSK3 & beta;-CREB/MMP-9 pathway.

Automated summary

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment, memory loss, and behavioral deficits. The aggregation of β-amyloid(1-42) (Aβ(1-42)) is a significant cause of AD pathogenesis. Despite extensive research, current treatment efficacy for AD remains insufficient. Nitric oxide (NO) has a neuroprotective role in the central nervous system by inhibiting Aβ aggregation and rescuing memory and learning deficits through the NO signaling pathway. Targeting the NO pathway may be a therapeutic option, but the limited half-life of NO in the biological system poses a challenge. This study explored a biomimetic dinitrosyl iron complex (DNIC-COOH) that can stably deliver NO to address this issue. Adding DNIC-COOH to neuron-like cells and primary cortical neurons along with Aβ(1-42) demonstrated its ability to protect neuronal cells, enhance neuronal functions, and facilitate Aβ(1-42) degradation through the NO-sGC-cGMP-AKT-GSK3β-CREB/MMP-9 pathway.