OXIDATIVE DAMAGE IN NEURODEGENERATION: ROLES IN THE PATHOGENESIS AND PROGRESSION OF ALZHEIMER DISEASE

Marzia Perluigi, Fabio Di Domenico, D. Allan Butterfield

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations

Abstract

Alzheimer disease (AD) is associated with multiple etiologies and pathological mechanisms, among which oxidative stress (OS) appears as a major determinant. Intriguingly, OS arises in various pathways regulating brain functions, and it seems to link different hypotheses and mechanisms of AD neuropathology with high fidelity. The brain is particularly vulnerable to oxidative damage, mainly because of its unique lipid composition, resulting in an amplified cascade of redox reactions that target several cellular components/functions ultimately leading to neurodegeneration. The present review highlights the “OS hypothesis of AD,” including amyloid beta-peptide-associated mechanisms, the role of lipid and protein oxidation unraveled by redox proteomics, and the antioxidant strategies that have been investigated to modulate the progression of AD. Collected studies from our groups and others have contributed to unraveling the close relationships between perturbation of redox homeostasis in the brain and AD neuropathology by elucidating redox-regulated events potentially involved in both the pathogenesis and progression of AD. However, the complexity of AD pathological mechanisms requires an in-depth understanding of several major intracellular pathways affecting redox homeostasis and relevant for brain functions. This understanding is crucial to developing pharmacological strategies targeting OS-mediated toxicity that may potentially contribute to slow AD progression as well as improve the quality of life of persons with this severe dementing disorder.

Original languageEnglish
Pages (from-to)103-197
Number of pages95
JournalPhysiological Reviews
Volume104
Issue number1
DOIs
StatePublished - Jan 2024

Bibliographical note

Publisher Copyright:
© 2024, American Physiological Society. All rights reserved.

Keywords

  • Ab and oxidative damage
  • Alzheimer disease and lipid peroxidation and protein oxidation
  • Alzheimer disease and translational approaches
  • Down syndrome and Alzheimer disease and oxidative stress
  • oxidative stress and energy dysmetabolism

ASJC Scopus subject areas

  • Physiology (medical)
  • Molecular Biology
  • Physiology

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