Peroxynitrite: A Potential Therapeutic Target for Alzheimer's Disease.

Abstract

The pathogenesis of Alzheimer's disease (AD) involves multiple pathological processes, including β-amyloid (Aβ) deposition, aberrant tau modification, oxidative stress, and neuroinflammation. The molecular interaction mechanism among them remains to be further clarified. Peroxynitrite (ONOO⁻) is a potent oxidizing and nitrating reactive nitrogen species formed from the rapid reaction between nitric oxide and superoxide. It mediates protein nitration, lipid peroxidation, and mitochondrial damage, thereby contributing to multiple pathological events in AD. This review outlines the physicochemical properties and biological behavior of ONOO⁻, and summarizes recent advances in detection techniques such as fluorescent probes and electrochemical sensors. It focuses on the role of ONOO⁻ within the AD pathological network and its interconnections with Aβ deposition, tau pathology, neuroinflammation, and blood-brain barrier disruption. Additionally, this review discusses the therapeutic potential of ONOO⁻-targeted strategies, aiming to provide novel insights into the crosstalk among multiple pathological pathways in Alzheimer's disease.