title: A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson's disease models.
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.
authors: 1] Department of Chemistry, National University of Singapore, Singapore 117543, Singapore [2].
authors: Lin
authors: L
authors: Li
authors: 1] Department of Research, National Neuroscience Institute, Singapore 308433, Singapore [2].
authors: Cheng-Wu
authors: CW
authors: Zhang
authors: Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
authors: Grace Y J
authors: GY
authors: Chen
authors: Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
authors: Biwei
authors: B
authors: Zhu
authors: Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
authors: Chou
authors: C
authors: Chai
authors: Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
authors: Qing-Hua
authors: QH
authors: Xu
authors: Department of Research, National Neuroscience Institute, Singapore 308433, Singapore.
authors: Eng-King
authors: EK
authors: Tan
authors: Institute of Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
authors: Qing
authors: Q
authors: Zhu
authors: 1] Department of Research, National Neuroscience Institute, Singapore 308433, Singapore [2] Duke-NUS Graduate Medical School, Singapore 169857, Singapore [3] Department of Physiology, National University of Singapore, Singapore 117543, Singapore.
authors: Kah-Leong
authors: KL
authors: Lim
authors: Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
authors: Shao Q
authors: SQ
authors: Yao
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D004330:Drosophila; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D015336:Molecular Probe Techniques; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism; D008995:Monoamine Oxidase / Q000032:analysis* / Q000378:metabolism; D010300:Parkinson Disease / Q000201:enzymology*
chemical_list: D015335:Molecular Probes; D008995:Monoamine Oxidase