Mitochondrial medicine: Neuroprotection and life extension by the new amphiphilic nitrone LPBNAH acting as a highly potent antioxidant agent

Burkhard Poeggeler, Grégory Durand, Ange Polidori, Miguel A. Pappolla, Ignacio Vega-Naredo, Ana Coto-Montes, Jutta Böker, Rüdiger Hardeland, Bernard Pucci

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The search for effective treatments that prevent oxidative stress associated with premature ageing and neurodegenerative diseases is an important area of neurochemical research. As age- and disease-related oxidative stress is frequently associated with mitochondrial dysfunction, amphiphilic antioxidant agents of high stability and selectivity that target these organelles can provide on-site protection. Such an amphiphilic nitrone protected human neuroblastoma cells at low micromolar concentrations against oxidative damage and death induced by exposure to the β-amyloid peptide, hydrogen peroxide and 3-hydroxykynurenine. Daily administration of the antioxidant at a concentration of only 5 μM significantly increased the lifespan of the individually cultured rotifer Philodina acuticornis odiosa Milne. This compound is unique in its exceptional anti-ageing efficacy, being one order of magnitude more potent than any other compound previously tested on rotifers. The nitrone protected these aquatic animals against the lethal toxicity of hydrogen peroxide and doxorubicin and greatly enhanced their survival when co-administered with these oxidotoxins. These findings indicate that amphiphilic antioxidants have a great potential as neuroprotective agents in preventing the death of cells and organisms exposed to enhanced oxidative stress and damage.

Original languageEnglish (US)
Pages (from-to)962-973
Number of pages12
JournalJournal of neurochemistry
Volume95
Issue number4
DOIs
StatePublished - Nov 2005
Externally publishedYes

Keywords

  • Ageing
  • Amyloid
  • Lifespan
  • Mitochondria
  • Radical scavenger
  • Rotifer

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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