Monitoring Early-Stage Protein Aggregation by an Aggregation-Induced Emission Fluorogen

2017 ◽  
Vol 89 (17) ◽  
pp. 9322-9329 ◽  
Author(s):  
Manjeet Kumar ◽  
Yuning Hong ◽  
David C. Thorn ◽  
Heath Ecroyd ◽  
John A. Carver
Keyword(s):  
Protein Aggregation ◽  
Early Stage ◽  
Aggregation Induced Emission

Fundamentals and Exploration of Aggregation-Induced Emission Molecules for Amyloid Protein Aggregation

2021 ◽  
Author(s):  
Yijing Tang ◽  
Dong Zhang ◽  
Yanxian Zhang ◽  
Yonglan Liu ◽  
Lirong Cai ◽  
...  
Keyword(s):  
Optical Properties ◽  
Protein Aggregation ◽  
Environmental Health ◽  
Amyloid Protein ◽  
Aggregation Induced Emission ◽  
The Past ◽  
Sensing Applications ◽  
Biomolecule Sensing

The past decade has witnessed the growing interest and advances in aggregation-induced emission (AIE) molecules as driven by their unique fluorescence/optical properties in particular sensing applications including biomolecule sensing/detection, environmental/health...

Structure-Based Design of Small Peptide Ligands to Inhibit Early-Stage Protein Aggregation Nucleation

2020 ◽  
Vol 60 (6) ◽  
pp. 3304-3314 ◽  
Author(s):  
Avinash Mishra ◽  
Rohit Bansal ◽  
Shravan Sreenivasan ◽  
Rozaleen Dash ◽  
Srishti Joshi ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Early Stage ◽  
Peptide Ligands ◽  
Small Peptide

scholarly journals When aggregation-induced emission meets protein aggregates

2021 ◽  
Author(s):  
Sicheng Tang ◽  
Songtao Ye ◽  
Xin Zhang
Keyword(s):  
Protein Aggregation ◽  
Protein Aggregates ◽  
Human Diseases ◽  
Diagnosis And Treatment ◽  
Live Cells ◽  
Future Application ◽  
Aggregation Process ◽  
Aggregation Induced Emission ◽  
Unmet Demand ◽  
Shed Light

There is an unmet demand for research tools to monitor the multistep protein aggregation process in live cells, a process that has been associated with a growing number of human diseases. Recently, AIEgens have been developed to directly monitor the entire protein aggregation process in test tubes and live cells. Future application of AIEgens is expected to shed light on both diagnosis and treatment of disease rooted in protein aggregation.

scholarly journals Bacterial production and direct functional screening of expanded molecular libraries for discovering inhibitors of protein aggregation

2019 ◽  
Vol 5 (10) ◽  
pp. eaax5108 ◽  
Author(s):  
Dafni C. Delivoria ◽  
Sean Chia ◽  
Johnny Habchi ◽  
Michele Perni ◽  
Ilias Matis ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Early Stage ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Functional Screening ◽  
Parkinson’S Diseases ◽  
Aggregation Inhibitors ◽  
Molecular Libraries

Protein misfolding and aggregation are associated with a many human disorders, including Alzheimer’s and Parkinson’s diseases. Toward increasing the effectiveness of early-stage drug discovery for these conditions, we report a bacterial platform that enables the biosynthesis of molecular libraries with expanded diversities and their direct functional screening for discovering protein aggregation inhibitors. We illustrate this approach by performing, what is to our knowledge, the largest functional screen of small-size molecular entities described to date. We generated a combinatorial library of ~200 million drug-like, cyclic peptides and rapidly screened it for aggregation inhibitors against the amyloid-β peptide (Aβ42), linked to Alzheimer’s disease. Through this procedure, we identified more than 400 macrocyclic compounds that efficiently reduce Aβ42 aggregation and toxicity in vitro and in vivo. Finally, we applied a combination of deep sequencing and mutagenesis analyses to demonstrate how this system can rapidly determine structure-activity relationships and define consensus motifs required for bioactivity.

The production of hydrogen peroxide during early-stage protein aggregation: a common pathological mechanism in different neurodegenerative diseases?

2005 ◽  
Vol 33 (4) ◽  
pp. 548-550 ◽  
Author(s):  
B.J. Tabner ◽  
S. Turnbull ◽  
N.J. Fullwood ◽  
M. German ◽  
D. Allsop
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Early Stage ◽  
Amyloid Β ◽  
Direct Production ◽  
Esr Spin Trapping ◽  
Pathological Mechanism ◽  
Aβ Amyloid ◽  
Production Of Hydrogen ◽  
Trapping Method

By means of an ESR spin-trapping method, we have shown that Aβ (amyloid β), α-synuclein and various toxic forms of the prion protein all appear to generate H2O2in vitro. A fundamental molecular mechanism underlying the pathogenesis of cell death in several different neurodegenerative diseases could be the direct production of H2O2 during the early stages of protein aggregation.

scholarly journals α-Synuclein expression and Nrf2 deficiency cooperate to aggravate protein aggregation, neuronal death and inflammation in early-stage Parkinson's disease

2012 ◽  
Vol 21 (14) ◽  
pp. 3173-3192 ◽  
Author(s):  
Isabel Lastres-Becker ◽  
Ayse Ulusoy ◽  
Nadia G. Innamorato ◽  
Gurdal Sahin ◽  
Alberto Rábano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Aggregation ◽  
Neuronal Death ◽  
Early Stage

Protein aggregation, metals and oxidative stress in neurodegenerative diseases

2005 ◽  
Vol 33 (5) ◽  
pp. 1082-1086 ◽  
Author(s):  
B.J. Tabner ◽  
O.M.A. El-Agnaf ◽  
M.J. German ◽  
N.J. Fullwood ◽  
D. Allsop
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Amyloid Fibrils ◽  
Early Stage ◽  
Redox Active ◽  
Active Metal ◽  
Future Therapy ◽  
And Oxidative Stress ◽  
Proteins And Peptides

There is clear evidence implicating oxidative stress in the pathology of many different neurodegenerative diseases. ROS (reactive oxygen species) are the primary mediators of oxidative stress and many of the aggregating proteins and peptides associated with neurodegenerative disease can generate hydrogen peroxide, a key ROS, apparently through interactions with redox-active metal ions. Our recent results suggest that ROS are generated during the very early stages of protein aggregation, when protofibrils or soluble oligomers are present, but in the absence of mature amyloid fibrils. The generation of ROS during early-stage protein aggregation may be a common, fundamental molecular mechanism underlying the pathogenesis of oxidative damage, neurodegeneration and cell death in several different neurodegenerative diseases. Drugs that specifically target this process could be useful in the future therapy of these diseases.

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