Development of indole-3-propionic acid (OXIGON™) for alzheimer’s disease

@article{Bendheim2002DevelopmentOI,
  title={Development of indole-3-propionic acid (OXIGON{\texttrademark}) for alzheimer’s disease},
  author={Paul E. Bendheim and Burkhard Poeggeler and Eyal Neria and Vivi Ziv and Miguel A Pappolla and Daniel G. Chain},
  journal={Journal of Molecular Neuroscience},
  year={2002},
  volume={19},
  pages={213-217}
}
The accumulation of amyloid-beta and concomitant oxidative stress are major pathogenic events in Alzheimer’s disease. Indole-3-propionic acid (IPA, OXIGON™) is a potent anti-oxidant devoid of pro-oxidant activity. IPA has been demonstrated to be an inhibitor of beta-amyloid fibril formation and to be a potent neuroprotectant against a variety of oxidotoxins. This review will summarize the known properties of IPA and outline the rationale behind its selection as a potential disease-modifying… 

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References

SHOWING 1-10 OF 38 REFERENCES

Potent Neuroprotective Properties against the Alzheimer β-Amyloid by an Endogenous Melatonin-related Indole Structure, Indole-3-propionic Acid*

In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals.

Vitamin E protects nerve cells from amyloid βprotein toxicity

Indole‐3‐propionic acid, a melatonin‐related molecule, protects hepatic microsomal membranes from iron‐induced oxidative damage: Relevance to cancer reduction

It is concluded that Fe3+‐induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA, however, IPA in high concentrations increase membrane fluidity.

Vitamin E protects nerve cells from amyloid beta protein toxicity.

It is shown here that ABP and an internal fragment encompassing residues 25 to 35 (beta 25-35) are cytotoxic to a clone of PC12 cells at concentrations above 1 x 10(-9)M and to several other cell lines at higher concentrations.

Oxidative injury in diseases of the central nervous system: focus on Alzheimer's disease.

Involvement of Oxidative Stress on the Impairment of Energy Metabolism Induced by Aβ Peptides on PC12 Cells: Protection by Antioxidants

Exposure of PC12 cells to A beta results in an impairment of energy metabolism, leading to a deficit in ATP levels and to the compromise of cellular viability, which seems to be a crucial event responsible for the energetic metabolic dysfunction induced by A beta.

Immunohistochemical evidence of antioxidant stress in Alzheimer's disease

The hypothesis that oxidative stress may be involved in the pathogenesis of Alzheimer's disease is supported.

Indole-3-propionate: a potent hydroxyl radical scavenger in rat brain

Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins.

It is hypothesized that impaired synaptic plasticity and associated memory dysfunction during early stage Alzheimer's disease and severe cellular degeneration and dementia during end stage could be caused by the biphasic impact of Abeta-derived diffusible ligands acting upon particular neural signal transduction pathways.

Increased Lipid Peroxidation Precedes Amyloid Plaque Formation in an Animal Model of Alzheimer Amyloidosis

Because LPO precedes amyloid plaque formation in Tg2576 mice, this suggests that brain oxidative damage contributes to AD pathogenesis before Aβ accumulation in the AD brain.