title: Two-Photon Enzymatic Probes Visualizing Sub-cellular/Deep-brain Caspase Activities in Neurodegenerative Models.
abstract: Caspases work as a double-edged sword in maintaining cell homeostasis. Highly regulated caspase activities are essential during animal development, but dysregulation might lead to different diseases, e.g. extreme caspase activation is known to promote neurodegeneration. At present, visualization of caspase activation has mostly remained at the cellular level, in part due to a lack of cell-permeable imaging probes capable of direct, real-time investigations of endogenous caspase activities in deep tissues. Herein, we report a suite of two-photon, small molecule/peptide probes which enable sensitive and dynamic imaging of individual caspase activities in neurodegenerative models under physiological conditions. With no apparent toxicity and the ability of imaging endogenous caspases both in different subcellular organelles of mammalian cells and in brain tissues, these probes serve as complementary tools to conventional histological analysis. They should facilitate future explorations of caspases at molecular, cellular and organism levels and inspire development of novel two-photon probes against other enzymes.
authors.affiliation: Department of Chemistry, National University of Singapore, 117543, Singapore.
authors.forename: Linghui
authors.initials: L
authors.lastname: Qian
authors.affiliation: Key Laboratory of Flexible Electronics &Institute of Advanced Materials, Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, 211816, P. R. China.|National Neuroscience Institute, 308433, Singapore.
authors.forename: Cheng-Wu
authors.initials: CW
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, National University of Singapore, 117543, Singapore.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Key Laboratory of Flexible Electronics &Institute of Advanced Materials, Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, 211816, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Chemistry, National University of Singapore, 117543, Singapore.
authors.forename: Nengyue
authors.initials: N
authors.lastname: Gao
authors.affiliation: National Neuroscience Institute, 308433, Singapore.
authors.forename: Kah-Leong
authors.initials: KL
authors.lastname: Lim
authors.affiliation: Department of Chemistry, National University of Singapore, 117543, Singapore.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Xu
authors.affiliation: Department of Chemistry, National University of Singapore, 117543, Singapore.
authors.forename: Shao Q
authors.initials: SQ
authors.lastname: Yao
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D020169:Caspases / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D036641:Microscopy, Fluorescence, Multiphoton; D008954:Models, Biological; D015335:Molecular Probes / Q000737:chemistry*; D051381:Rats
chemical_list: D015335:Molecular Probes; D020169:Caspases