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

Bendheim, Paul E.; Pöeggeler, Burkhard; Neria, Eyal; Ziv, Vivi; Pappolla, Miguel A.; Chain, Daniel G.

doi:10.1007/s12031-002-0036-0

Cited by 145 publications

(99 citation statements)

References 29 publications

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“…Conversely, a different set of enteric bacteria has been implicated in the metabolic transformation of indole to indole-3-propionic acid (IPA) (27). IPA, also identified only in the plasma of conv mice, has been shown to be a powerful antioxidant (28), and is currently being investigated as a possible treatment for Alzheimer's disease (29,30).…”

Section: Resultsmentioning

confidence: 99%

Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites

Wikoff

Anfora²,

Li³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

2,327

1,878

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Although it has long been recognized that the enteric community of bacteria that inhabit the human distal intestinal track broadly impacts human health, the biochemical details that underlie these effects remain largely undefined. Here, we report a broad MS-based metabolomics study that demonstrates a surprisingly large effect of the gut ''microbiome'' on mammalian blood metabolites. Plasma extracts from germ-free mice were compared with samples from conventional (conv) animals by using various MS-based methods. Hundreds of features were detected in only 1 sample set, with the majority of these being unique to the conv animals, whereas Ϸ10% of all features observed in both sample sets showed significant changes in their relative signal intensity. Amino acid metabolites were particularly affected. For example, the bacterial-mediated production of bioactive indole-containing metabolites derived from tryptophan such as indoxyl sulfate and the antioxidant indole-3-propionic acid (IPA) was impacted. Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes. Multiple organic acids containing phenyl groups were also greatly increased in the presence of gut microbes. A broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome was observed, suggesting that the gut microflora has a direct impact on the drug metabolism capacity of the host. Together, these results suggest a significant interplay between bacterial and mammalian metabolism.

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Section: Resultsmentioning

confidence: 99%

Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites

Wikoff

Anfora²,

Li³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

2,327

1,878

View full text Add to dashboard Cite

show abstract

“…IPA has been shown to be a powerful antioxidant [71] and has been considered as a possible treatment for Alzheimer's disease [72] due to its ability to protect neurons and neuroblastoma cells against oxidative damage and death [73,74].…”

Section: Indole-3-propionic Acidmentioning

confidence: 99%

Bacterial Neuroactive Compounds Produced by Psychobiotics

Wall

Cryan

Ross

et al. 2014

Advances in Experimental Medicine and Biology

276

156

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We recently coined the phrase 'psychobiotics' to describe an emerging class of probiotics of relevance to psychiatry [Dinan et al., Biol Psychiatry 2013;74(10):720-726]. Such "mind-altering" probiotics may act via their ability to produce various biologically active compounds, such as peptides and mediators normally associated with mammalian neurotransmission. Several molecules with neuroactive functions such as gamma-aminobutyric acid (GABA), serotonin, catecholamines and acetylcholine have been reported to be microbially-derived, many of which have been isolated from bacteria within the human gut. Secreted neurotransmitters from bacteria in the intestinal lumen may induce epithelial cells to release molecules that in turn modulate neural signalling within the enteric nervous system and consequently signal brain function and behaviour of the host. Consequently, neurochemical containing/producing probiotic bacteria may be viewed as delivery vehicles for neuroactive compounds and as such, probiotic bacteria may possibly have the potential as a therapeutic strategy in the prevention and/or treatment of certain neurological and neurophysiological conditions.

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“…Pharmacological studies of indolic compounds reported a wide variety of important biological properties such as anti-inflammatory [2,3], analgesic [3], antibacterial [4], antifungal [5], neuroprotective [6,7], antitumour [8][9][10] and antioxidant properties [11].…”

Section: Introductionmentioning

confidence: 99%

Pathways of Electrochemical Oxidation of Indolic Compounds

2011

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The electrochemical behaviour of indole and a group of indole-containing compounds with a substituent at the C3 position, indol-3-acetamide (IAM), tryptamine, gramine, indole acetic acid (IAA), indole propionic acid (IPA), indole butyric acid (IBA) and tryptophan, was investigated at a glassy carbon electrode, in order to determine their oxidation pathways. Indole undergoes one irreversible pH dependent oxidation, whereas the oxidation process of indole derivatives was more complex, a two step, the oxidation at C2 position on the pyrrole ring followed by the hydroxylation at the C7 position of the benzene moiety of indoles, irreversible pH dependent oxidation.

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

Cited by 145 publications

References 29 publications

Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites

Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites

Bacterial Neuroactive Compounds Produced by Psychobiotics

Pathways of Electrochemical Oxidation of Indolic Compounds

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