Tocovid Attenuated Oxidative Stress and Cognitive Decline by Inhibiting Amyloid-β-Induced NOX2 Activation in Alzheimer's Disease Mice

J Alzheimers Dis. 2024;99(s1):S23-S33. doi: 10.3233/JAD-220761.

Abstract

Background: NADPH oxidase 2 (NOX2) is an important source of reactive oxygen species (ROS). Activated NOX2 may contribute to Alzheimer's disease (AD). Our previous studies showed that a novel vitamin E mixture, Tocovid, had potential neuroprotective effects in a stroke mice model and an AD cell model.

Objective: The aim of this study was two-fold: to assess whether long-term Tocovid treatment can regulate NOX2, and the therapeutic effects of long-term administration of Tocovid to an AD mice model.

Methods: Therapeutic effects of long-term administration of Tocovid (200 mg/kg /day) on an Aβ-overexpressed transgenic AD mice model (APP23, n = 8) was investigated. The therapeutic effect of Tocovid in 16-month-old mice compared with the no-treatment APP23 group (n = 9) was assessed.

Results: Tocovid treatment strongly improved motor and memory deficits of APP23 mice by attenuating NOX2 expression, oxidative stress, neuroinflammation, neurovascular unit dysfunction, synaptic alteration, and Aβ deposition after 16 months.

Conclusion: These findings suggest that NOX2 is a potential target in AD pathology. Long-term administration of Tocovid may be a promising candidate for AD treatment.

Keywords: Alzheimer’s disease; NOX2; Tocovid; cerebral amyloid angiopathy; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides* / metabolism
  • Animals
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / metabolism
  • Disease Models, Animal*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic*
  • NADPH Oxidase 2* / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress* / drug effects

Substances

  • NADPH Oxidase 2
  • Amyloid beta-Peptides
  • Cybb protein, mouse
  • Neuroprotective Agents