A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson’s disease models

Lin Li, Cheng-Wu Zhang, Grace Y. J. Chen, Biwei Zhu, Chou Chai, Qing-Hua Xu, Eng-King Tan, Qing Zhu, Kah-Leong Lim () and Shao Q. Yao ()
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Lin Li: National University of Singapore
Cheng-Wu Zhang: National Neuroscience Institute
Grace Y. J. Chen: National University of Singapore
Biwei Zhu: National University of Singapore
Chou Chai: Duke-NUS Graduate Medical School
Qing-Hua Xu: National University of Singapore
Eng-King Tan: National Neuroscience Institute
Qing Zhu: Institute of Bioengineering, Zhejiang University of Technology
Kah-Leong Lim: National Neuroscience Institute
Shao Q. Yao: National University of Singapore

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract The unusually high MAO-B activity consistently observed in Parkinson’s disease (PD) patients has been proposed as a biomarker; however, this has not been realized due to the lack of probes suitable for MAO-B-specific detection in live cells/tissues. Here we report the first two-photon, small molecule fluorogenic probe (U1) that enables highly sensitive/specific and real-time imaging of endogenous MAO-B activities across biological samples. We also used U1 to confirm the reported inverse relationship between parkin and MAO-B in PD models. With no apparent toxicity, U1 may be used to monitor MAO-B activities in small animals during disease development. In clinical samples, we find elevated MAO-B activities only in B lymphocytes (not in fibroblasts), hinting that MAO-B activity in peripheral blood cells might be an accessible biomarker for rapid detection of PD. Our results provide important starting points for using small molecule imaging techniques to explore MAO-B at the organism level.

Date: 2014
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DOI: 10.1038/ncomms4276

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