Advanced Oxidative Protein Products Role in Multiple Sclerosis: a Systematic Review and Meta-analysis

Mol Neurobiol. 2021 Nov;58(11):5724-5742. doi: 10.1007/s12035-021-02493-9. Epub 2021 Aug 15.


Multiple sclerosis (MS) is an autoimmune-mediated disease that damages the central nervous system. MS pathophysiological features are not entirely understood, but the increase of reactive oxygen species (ROS) possibly causes myelin and oligodendrocyte degeneration. ROS-increased production generates new compounds through oxidative modifications, including advanced oxidative protein products (AOPPs). The AOPPs are oxidative stress biomarkers and inflammatory mediators commonly formed by hypochlorous acid oxidative action on albumin. Considering that AOPPs accumulation produces ROS and induces neuronal apoptosis, these may represent a new target for drug development to MS treatment and a possible biomarker to monitor the severity of the disease. Thus, this review aims to investigate if there is an alteration in the AOPPs levels in MS and its possible involvement in patient disability. The second objective is to analyze whether drugs or compounds used in MS treatment could modify the AOPPs levels. The protocol was registered in PROSPERO (CRD42020203268). The databases' search yielded 327 articles. We excluded 259 duplicated articles and evaluated 68 articles by the title and abstract. We full-text analyzed 17 articles and included 13 articles. The AOPPs levels were increased in not-treated MS patients. Furthermore, the increase in disability status was associated with AOPPs accumulation in not-treated MS patients. Additionally, the AOPPs levels were reduced in MS patients after treatment. Therefore, AOPPs seem to play a role in MS pathophysiology and may become a new target for drug development and help MS diagnosis or treatment follow-up.

Keywords: Albumin; Apoptosis; Disability; Myeloperoxidase; Neuroinflammation; Neuropathic pain.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Advanced Oxidation Protein Products / blood*
  • Apoptosis
  • Biomarkers / blood
  • Case-Control Studies
  • Clinical Trials as Topic
  • Cross-Sectional Studies
  • Drug Development
  • Humans
  • Inflammation
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / drug therapy
  • Oxidative Stress
  • Reactive Oxygen Species


  • Advanced Oxidation Protein Products
  • Biomarkers
  • Reactive Oxygen Species