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Intermediates involved in serotonin oxidation catalyzed by Cu bound Aβ peptides.

ABSTRACT: The degradation of neurotransmitters is a hallmark feature of Alzheimer's disease (AD). Copper bound Aβ peptides, invoked to be involved in the pathology of AD, are found to catalyze the oxidation of serotonin (5-HT) by H₂O₂. A combination of EPR and resonance Raman spectroscopy reveals the formation of a Cu(ii)-OOH species and a dimeric, EPR silent, Cu₂O₂ bis-μ-oxo species under the reaction conditions. The Cu(ii)-OOH species, which can be selectively formed in the presence of excess H₂O₂, is the reactive intermediate responsible for 5-HT oxidation. H₂O₂ produced by the reaction of O₂ with reduced Cu(i)-Aβ species can also oxidize 5-HT. Both these pathways are physiologically relevant and may be involved in the observed decay of neurotransmitters as observed in AD patients.

SUBMITTER: Nath AK

PROVIDER: S-EPMC8179298 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Intermediates involved in serotonin oxidation catalyzed by Cu bound Aβ peptides.

Nath Arnab Kumar AK Ghatak Arnab A Dey Abhishek A Dey Somdatta Ghosh SG

Chemical science 20201222 5

The degradation of neurotransmitters is a hallmark feature of Alzheimer's disease (AD). Copper bound Aβ peptides, invoked to be involved in the pathology of AD, are found to catalyze the oxidation of serotonin (5-HT) by H2O2. A combination of EPR and resonance Raman spectroscopy reveals the formation of a Cu(ii)-OOH species and a dimeric, EPR silent, Cu2O2 bis-μ-oxo species under the reaction conditions. The Cu(ii)-OOH species, which can be selectively ...[more]

PMID: 34163956

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