Novel Pentameric Thiophene Derivatives for in Vitro and in Vivo Optical Imaging of a Plethora of Protein Aggregates in Cerebral Amyloidoses Export

@article{Aslund2009, abstract = {Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying cerebral amyloidoses. Here we report the chemical design of pentameric thiophene derivatives, denoted luminescent conjugated oligothiophenes (LCOs), which could be used for real-time visualization of cerebral protein aggregates in transgenic mouse models of neurodegenerative diseases by multiphoton microscopy. One of the LCOs, p-FTAA, could be utilized for ex vivo spectral assignment of distinct prion deposits from two mouse-adapted prion strains. p-FTAA also revealed staining of transient soluble pre-fibrillar non-thioflavinophilic Aβ-assemblies during in vitro fibrillation of Aβ peptides. In brain tissue samples, Aβ deposits and neurofibrillary tangles (NFTs) were readily identified by a strong fluorescence from p-FTAA and the LCO staining showed complete co-localization with conventional antibodies (6E10 and AT8). In addition, a patchy islet-like staining of individual Aβ plaque was unveiled by the anti-oligomer A11 antibody during co-staining with p-FTAA. The major hallmarks of Alzheimer's disease, namely, Aβ aggregates versus NFTs, could also be distinguished because of distinct emission spectra from p-FTAA. Overall, we demonstrate that LCOs can be utilized as powerful practical research tools for studying protein aggregation diseases and facilitate the study of amyloid origin, evolution and maturation, Aβ–tau interactions, and pathogenesis both ex vivo and in vivo.}, author = {\r{A}slund, Andreas and Sigurdson, Christina J. and Klingstedt, Therése and Grathwohl, Stefan and Bolmont, Tristan and Dickstein, Dara L. and Glimsdal, Eirik and Prokop, Stefan and Lindgren, Mikael and Konradsson, Peter and Holtzman, David M. and Hof, Patrick R. and Heppner, Frank L. and Gandy, Samuel and Jucker, Mathias and Aguzzi, Adriano and Hammarström, Per and Nilsson}, citeulike-article-id = {5831076}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/cb900112v}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/cb900112v}, day = {21}, doi = {10.1021/cb900112v}, journal = {ACS Chemical Biology}, keywords = {amyloid, disease, dyes, fluorescence}, month = {August}, number = {8}, pages = {673--684}, posted-at = {2009-09-23 14:19:34}, priority = {2}, title = {Novel Pentameric Thiophene Derivatives for in Vitro and in Vivo Optical Imaging of a Plethora of Protein Aggregates in Cerebral Amyloidoses}, url = {http://dx.doi.org/10.1021/cb900112v}, volume = {4}, year = {2009} }

TY - JOUR ID - Aslund2009 L3 - citeulike-article-id:5831076 N2 - Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying cerebral amyloidoses. Here we report the chemical design of pentameric thiophene derivatives, denoted luminescent conjugated oligothiophenes (LCOs), which could be used for real-time visualization of cerebral protein aggregates in transgenic mouse models of neurodegenerative diseases by multiphoton microscopy. One of the LCOs, p-FTAA, could be utilized for ex vivo spectral assignment of distinct prion deposits from two mouse-adapted prion strains. p-FTAA also revealed staining of transient soluble pre-fibrillar non-thioflavinophilic Aβ-assemblies during in vitro fibrillation of Aβ peptides. In brain tissue samples, Aβ deposits and neurofibrillary tangles (NFTs) were readily identified by a strong fluorescence from p-FTAA and the LCO staining showed complete co-localization with conventional antibodies (6E10 and AT8). In addition, a patchy islet-like staining of individual Aβ plaque was unveiled by the anti-oligomer A11 antibody during co-staining with p-FTAA. The major hallmarks of Alzheimer's disease, namely, Aβ aggregates versus NFTs, could also be distinguished because of distinct emission spectra from p-FTAA. Overall, we demonstrate that LCOs can be utilized as powerful practical research tools for studying protein aggregation diseases and facilitate the study of amyloid origin, evolution and maturation, Aβ–tau interactions, and pathogenesis both ex vivo and in vivo. IS - 8 JF - ACS Chemical Biology EP - 684 TI - Novel Pentameric Thiophene Derivatives for in Vitro and in Vivo Optical Imaging of a Plethora of Protein Aggregates in Cerebral Amyloidoses VL - 4 SP - 673 KW - amyloid KW - disease KW - dyes KW - fluorescence AU - Åslund, Andreas AU - Sigurdson, Christina AU - Klingstedt, Therése AU - Grathwohl, Stefan AU - Bolmont, Tristan AU - Dickstein, Dara AU - Glimsdal, Eirik AU - Prokop, Stefan AU - Lindgren, Mikael AU - Konradsson, Peter AU - Holtzman, David AU - Hof, Patrick AU - Heppner, Frank AU - Gandy, Samuel AU - Jucker, Mathias AU - Aguzzi, Adriano AU - Hammarström, Per AU - Nilsson PY - 2009/08/21/ UR - http://dx.doi.org/10.1021/cb900112v ER -