scholarly journals Inhibition of Protein Misfolding/Aggregation Using Polyglutamine Binding Peptide QBP1 as a Therapy for the Polyglutamine Diseases

2013 ◽  
Vol 10 (3) ◽  
pp. 440-446 ◽  
Author(s):  
H. Akiko Popiel ◽  
Toshihide Takeuchi ◽  
James R. Burke ◽  
Warren J. Strittmatter ◽  
Tatsushi Toda ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Polyglutamine Diseases ◽  
Binding Peptide

SynB3 conjugated QBP1 passes blood-brain barrier models and inhibits polyQ protein aggregation

2021 ◽  
Vol 29 ◽  
Author(s):  
Lingyan Zuo ◽  
Weiqian Li ◽  
Jifang Shi ◽  
Yingzhen Su ◽  
Hongyan Shuai ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Blood Brain Barrier ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Polyglutamine Diseases ◽  
Binding Peptide ◽  
Blood Brain ◽  
Cell Penetrating ◽  
Pass Through ◽  
Polyglutamine Protein

Background: Polyglutamine diseases are degenerative diseases in the central nervous system caused by CAG trinucleotide repeat expansion which encodes polyglutamine tracts, leading to the misfolding of pathological proteins. Small peptides can be designed to prevent polyglutamine diseases by inhibiting the polyglutamine protein aggregation, for example, polyglutamine binding peptide 1(QBP1). However, the transportation capability of polyglutamine binding peptide 1 across the blood-brain barrier is less efficient. We hypothesized whether its therapeutic effect could be improved by increasing the rate of membrane penetration. Objectives: The objective of the study was to explore whether polyglutamine binding peptide 1 conjugated cell-penetrating peptides could pass through the blood-brain barrier and inhibit the aggregation of polyglutamine proteins. Methods: n order to investigate the toxic effects, we constructed a novel stable inducible PC12 cells to express Huntington protein that either has 11 glutamine repeats or 63 glutamine repeats to mimic wild type and polyglutamine expand Huntington protein, respectively. Both SynB3 and TAT conjugated polyglutamine binding peptide 1 was synthesized, respectively, and we tested their capabilities to pass through a Trans-well system and subsequently studied the counteractive effects on polyglutamine protein aggregation. Results: The conjugation of cell-penetrating peptides to SynB3 and TAT enhanced the transportation of polyglutamine binding peptide 1 across the mono-cell layer and ameliorated polyglutamine-expanded Huntington protein aggregation; moreover, SynB3 showed better delivery efficiency than TAT. Interestingly, it has been observed that polyglutamine binding peptide 1 specifically inhibited polyglutamine-expanded protein aggregation rather than affected other amyloidosis proteins, for example, β-Amyloid. Conclusion: Our study indicated that SynB3 could be an effective carrier for polyglutamine binding peptide 1 distribution through the blood-brain barrier model and ameliorate the formation of polyglutamine inclusions, thus SynB3 conjugated polyglutamine binding peptide 1 could be considered as a therapeutic candidate for polyglutamine diseases.

Dimethyl-sulfoxide is a Suitable Solvent for Fluorescent Microscopy Detection of Medium and Strong Heat Shock Inductors Using Transgenic Zebrafish

2018 ◽  
Vol 69 (2) ◽  
pp. 337-340
Author(s):  
Vlad Preluca ◽  
Bogdan Horatiu Serb ◽  
Sanda Marchian ◽  
Diter Atasie ◽  
Mihaela Cernusca Mitariu ◽  
...  
Keyword(s):  
Heat Shock ◽  
Dimethyl Sulfoxide ◽  
Heat Shock Response ◽  
Protein Misfolding ◽  
Fluorescent Microscopy ◽  
Screening Tests ◽  
Transgenic Zebrafish ◽  
Fluorescent Intensity ◽  
Shock Response ◽  
Heat Shock Induction

Heat shock inductors have potential as treatment for degenerative and protein misfolding diseases. Dimethyl-sulfoxide is widely used as a solvent in pharmacological screening tests and has been shown to have heat shock induction effects. Transgenic Tg (hsp70l:EGFP-HRAS_G12V)io3(AB) zebrafish larvae were exposed for 24 hours to dimethyl-sulfoxide in concentratios of 0.1-2%, and to moderate heat shock inductors pentoxifylline and tacrolimus. Positive controls were exposed to 35, 38 and 40�C for 20 min, and incubated for 24 h at 28�C. Heat shock response was measured by fluorescence microscopy and signal intensity quantification in FIJI. Dimethyl-sulfoxide caused a dose-dependant increase in fluorescent intensity, but significantly lower compared with exposure to 38 and 40�C. Pentoxifylline and tacrolimus induced a significantly higher increase in fluorescence compared with 0.5% dimethyl-sulfoxide. Thus, although dimethyl-sulfoxide has independent heat shock induction effects, concentrations of up to 0.5% are suitable for heat shock response screening tests.

Manufacturing of Iron Binding Peptide Using Sericin Hydrolysate and Its Bioavailability in Iron Deficient Rat

2010 ◽  
Vol 39 (10) ◽  
pp. 1446-1451 ◽  
Author(s):  
Hye-Jin Cho ◽  
Hyun-Sun Lee ◽  
Eun-Young Jung ◽  
So-Yeon Park ◽  
Woo-Taek Lim ◽  
...  
Keyword(s):  
Iron Binding ◽  
Binding Peptide ◽  
Iron Deficient

Isolation of a Calcium-binding Peptide from Chlorella Protein Hydrolysates

2010 ◽  
Vol 15 (4) ◽  
pp. 282-286 ◽  
Author(s):  
So-Jeong Jeon ◽  
Ji-Hye Lee ◽  
Kyung-Bin Song
Keyword(s):  
Calcium Binding ◽  
Protein Hydrolysates ◽  
Binding Peptide

Peptide-Based Therapeutic Approaches for Treatment of the Polyglutamine Diseases

2014 ◽  
Vol 21 (23) ◽  
pp. 2575-2582 ◽  
Author(s):  
Toshihide Takeuchi ◽  
H. Popiel ◽  
Shiroh Futaki ◽  
Keiji Wada ◽  
Yoshitaka Nagai
Keyword(s):  
Polyglutamine Diseases ◽  
Therapeutic Approaches

Microbial Genetic Screens for Monitoring Protein Misfolding Associated with Neurodegeneration: Tools for Identifying Disease-Relevant Genes and for Screening Synthetic and Natural Compound Libraries for the Discovery of Potential Therapeutics

2018 ◽  
Vol 24 (19) ◽  
pp. 2055-2075 ◽  
Author(s):  
Kalliopi Kostelidou ◽  
Ilias Matis ◽  
Georgios Skretas
Keyword(s):  
Protein Misfolding ◽  
Socioeconomic Impact ◽  
Genetic Screens ◽  
Subsequent Formation ◽  
The Past ◽  
Compound Libraries ◽  
Selection Systems ◽  
Cellular Factors ◽  
Effective Drugs ◽  
Potential Therapeutics

Neurodegenerative Diseases (ND) are a major threat to the aging population and the lack of a single preventive or disease-modifying agent only serves to increase their impact. In the past few years, protein misfolding and the subsequent formation of neurotoxic oligomeric/aggregated protein species have emerged as a unifying theme underlying the pathology of these complex diseases. Recently developed microbial genetic screens and selection systems for monitoring ND-associated protein misfolding have allowed the establishment of highthroughput assays for the identification of cellular factors and processes that are important mediators of NDassociated proteotoxicities. In addition, such systems have facilitated the discovery of synthetic and natural compounds with the ability to rescue the misfolding and the associated pathogenic effects of aggregation-prone proteins associated with NDs. This review outlines such available systems in bacteria and yeast, whose usage will likely accelerate the pre-clinical discovery process for effective drugs against a variety of NDs with high socioeconomic impact.

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