Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-26929

Aslund, A; Sigurdson, C J; Klingstedt, T; Grathwohl, S; Bolmont, T; Dickstein, D L; Glimsdal, E; Prokop, S; Lindgren, M; Konradsson, P; Holtzman, D M; Hof, P R; Heppner, F L; Gandy, S; Jucker, M; Aguzzi, A; Hammarström, P; Nilsson, K P R (2009). Novel pentameric thiophene derivatives for in vitro and in vivo optical imaging of a plethora of protein aggregates in cerebral amyloidoses. ACS Chemical Biology, 4(8):673-684.

[img] PDF - Registered users only
5MB

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 Abeta-assemblies during in vitro fibrillation of Abeta peptides. In brain tissue samples, Abeta 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 Abeta plaque was unveiled by the anti-oligomer A11 antibody during co-staining with p-FTAA. The major hallmarks of Alzheimer's disease, namely, Abeta 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, Abeta-tau interactions, and pathogenesis both ex vivo and in vivo.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:10 Jan 2010 10:50
Last Modified:30 Nov 2013 22:58
Publisher:American Chemical Society
ISSN:1554-8929
Publisher DOI:10.1021/cb900112v
PubMed ID:19624097
Citations:Web of Science®. Times Cited: 70
Google Scholar™
Scopus®. Citation Count: 77

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page