Luminescent conjugated poly- and oligo-thiophenes: optical ligands for spectral assignment of a plethora of protein aggregates

2012 ◽  
Vol 40 (4) ◽  
pp. 704-710 ◽  
Author(s):  
Therése Klingstedt ◽  
K. Peter R. Nilsson

The deposition of protein aggregates in various parts of our body gives rise to several devastating diseases, and the development of probes for the selective detection of aggregated proteins is crucial to advance our understanding of the pathogenesis underlying these diseases. LCPs (luminescent conjugated polythiophenes) are fluorescent probes that bind selectively to protein aggregates. The conjugated thiophene backbone is flexible and offers a connection between the conformation and the emission properties, hence binding of LCPs gives the molecule a spectral fingerprint. The present review covers the utilization of LCPs to study the heterogeneity of protein aggregates. It emphasizes specifically the introduction of well-defined probes called LCOs (luminescent conjugated oligothiophenes) and reports how these molecules can be used for real-time in vivo imaging of cerebral plaques as well as for spectral discrimination of protein aggregates and detection of early species in the fibrillation pathway of amyloid β-peptide.

2016 ◽  
Vol 88 (3) ◽  
pp. 1944-1950 ◽  
Author(s):  
Hualong Fu ◽  
Peiyu Tu ◽  
Liu Zhao ◽  
Jiapei Dai ◽  
Boli Liu ◽  
...  

2014 ◽  
Vol 56 ◽  
pp. 69-83 ◽  
Author(s):  
Ko-Fan Chen ◽  
Damian C. Crowther

The formation of amyloid aggregates is a feature of most, if not all, polypeptide chains. In vivo modelling of this process has been undertaken in the fruitfly Drosophila melanogaster with remarkable success. Models of both neurological and systemic amyloid diseases have been generated and have informed our understanding of disease pathogenesis in two main ways. First, the toxic amyloid species have been at least partially characterized, for example in the case of the Aβ (amyloid β-peptide) associated with Alzheimer's disease. Secondly, the genetic underpinning of model disease-linked phenotypes has been characterized for a number of neurodegenerative disorders. The current challenge is to integrate our understanding of disease-linked processes in the fly with our growing knowledge of human disease, for the benefit of patients.


2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.


APOPTOSIS ◽  
2010 ◽  
Vol 16 (2) ◽  
pp. 198-207 ◽  
Author(s):  
Matteo Scabini ◽  
Fabio Stellari ◽  
Paolo Cappella ◽  
Sara Rizzitano ◽  
Gemma Texido ◽  
...  

2010 ◽  
Vol 48 (1) ◽  
pp. 136-144 ◽  
Author(s):  
D. Allan Butterfield ◽  
Veronica Galvan ◽  
Miranda Bader Lange ◽  
Huidong Tang ◽  
Renã A. Sowell ◽  
...  

2021 ◽  
Vol 103-B (7 Supple B) ◽  
pp. 9-16
Author(s):  
William J. Hadden ◽  
Mazen Ibrahim ◽  
Mariam Taha ◽  
Kerstin Ure ◽  
Yun Liu ◽  
...  

Aims The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Chu Hsien Lim ◽  
Prameet Kaur ◽  
Emelyne Teo ◽  
Vanessa Yuk Man Lam ◽  
Fangchen Zhu ◽  
...  

The brains of Alzheimer’s disease patients show a decrease in brain mass and a preponderance of extracellular Amyloid-β plaques. These plaques are formed by aggregation of polypeptides that are derived from the Amyloid Precursor Protein (APP). Amyloid-β plaques are thought to play either a direct or an indirect role in disease progression, however the exact role of aggregation and plaque formation in the aetiology of Alzheimer’s disease (AD) is subject to debate as the biological effects of soluble and aggregated Amyloid-β peptides are difficult to separate in vivo. To investigate the consequences of formation of Amyloid-β oligomers in living tissues, we developed a fluorescently tagged, optogenetic Amyloid-β peptide that oligomerizes rapidly in the presence of blue light. We applied this system to the crucial question of how intracellular Amyloid-β oligomers underlie the pathologies of A. We use Drosophila, C. elegans and D. rerio to show that, although both expression and induced oligomerization of Amyloid-β were detrimental to lifespan and healthspan, we were able to separate the metabolic and physical damage caused by light-induced Amyloid-β oligomerization from Amyloid-β expression alone. The physical damage caused by Amyloid-β oligomers also recapitulated the catastrophic tissue loss that is a hallmark of late AD. We show that the lifespan deficit induced by Amyloid-β oligomers was reduced with Li+ treatment. Our results present the first model to separate different aspects of disease progression.


2006 ◽  
Vol 1 (1) ◽  
pp. 476-485 ◽  
Author(s):  
Blandine Franke-Fayard ◽  
Andrew P Waters ◽  
Chris J Janse

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