Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 283, Issue 46, Pages 31657-31664Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M804722200
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Funding
- National Natural Science Foundation of China [20825206, 20672067]
- Australian Research Council Federation
- National Health and Medical Research Council
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Decelerated degradation of beta-amyloid (A beta) and its interaction with synaptic copper may be pathogenic in Alzheimer disease. Recently, Co(III)-cyclen tagged to an aromatic recognition motif was shown to degrade A beta in vitro. Here, we report that apocyclen attached to selective A beta recognition motifs (KLVFF or curcumin) can capture copper bound to A beta and use the Cu(II) in place of Co(III) to become proteolytically active. The resultant complexes interfere with A beta aggregation, degrade A beta into fragments, preventing H2O2 formation and toxicity in neuronal cell culture. Because A beta binds Cu in amyloid plaques, apocyclen-tagged targeting molecules may be a promising approach to the selective degradation of A beta in Alzheimer disease. The principle of copper capture generalize to other amyloidoses where copper is implicated.
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