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Myeloperoxidase as a therapeutic target for oxidative damage in Alzheimer’s disease

Astrid Mayleth Rivera Antonio, Itzia I. Padilla‐Martínez, Mónica Torres-Ramos, Martha Cecilia Rosales‐Hernández

2025Journal of Enzyme Inhibition and Medicinal Chemistry16 citationsDOIOpen Access PDF

Abstract

Alzheimer's disease (AD) is a major neurodegenerative disorder more common in older adults. One of the leading AD hypotheses involves the amyloid beta (A) production, it is associated to oxidative stress, neuroinflammation, and neurovascular damage. The interaction of A with the blood vessel wall contributes to the disruption of the blood-brain barrier (BBB), allowing neutrophil infiltration containing the myeloperoxidase enzyme (MPO), which produces hypochlorous acid (HOCl) a potent oxidant. Also, MPO could be released from the microglia cells and interact with the amyloid beta plaques. This review aims to study the role of MPO in the progression of AD, in particular its contribution to oxidative stress and neuroinflammation. Furthermore, to explore the MPO-potential as AD-biomarker to evaluate the therapeutic potential of its inhibitors to mitigate the neurotoxicity. Finally, revise MPO inhibitors that could act as dual inhibitors acting on MPO and acetylcholinesterase and or another target involved in AD.

Topics & Concepts

MyeloperoxidaseOxidative damageDiseaseOxidative stressOxidative phosphorylationMedicineAlzheimer's diseaseChemistryImmunologyInflammationBiochemistryInternal medicineNeutrophil, Myeloperoxidase and Oxidative MechanismsAdvanced Glycation End Products researchNeuroinflammation and Neurodegeneration Mechanisms
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