Huntington's disease (HD) is classified as a protein‐misfolding disease correlated with the mutant Huntingtin (mHtt) protein with abnormally expanded polyglutamine (polyQ) domains. Because no effective drugs have yet been reported, attempts to develop better therapy to delay the age of onset are in urgent demand. In this study, an amphiphilic peptide consisting of negatively charged hexaglutamic acid and a stretch of decaglutamine (E6Q10) was chemically synthesized as an inhibitor against polyQ and mHtt toxicity. It is found that E6Q10 selfassembles into spherical vesicles, as shown by means of TEM, cryoelectron microscopy, and dynamic light scattering. Assembled E6Q10 prevented the polyQ‐rich peptide (KKWQ20AKK) from forming amyloid fibrils. To enable the cell‐penetration ability of E6Q10, the E6Q10⋅chitosan complex was generated. It is demonstrated that the complex penetrates cells, interferes with the mHtt oligomerization and aggregation process, and prevents mHtt cytotoxicity. By combining positively charged chitosan and amphiphilic peptides with a negatively charge moiety, a new strategy is provided to develop biocompatible and biodegradable inhibitors against mHtt toxicity.
This research aims to find out how the practice of collaborating with rice processing in the Tamanagung Village, Cluring District, Banyuwangi, and knowing how to practice the cooperation with processing of maro in The Tamanagung Village, Cluring District, Banyuwangi the perspective of Islamic economic law. The type used in this study is descriptive analysis, which describes the data that researchers collect both from observations, interviews and documentation. Data analysis uses interactive model analysis techniques. The results of the study are the collaboration carried out by the owner of the paddy field and the paddy farmer, the paddy owner only provides land only, while the paddy cultivator is burdened with material capital and labor to work on the paddy. The practice of maro processing in paddy fields in Tamanagung Village, Cluring District, Banyuwangi Regency is included in the mukhabarah contract. The profit sharing mechanism uses the bawon system (fee). If 100% of the yield is obtained, 20% will be given to the cultivators of the paddy fields, while the remaining 80% of the deduction will be collected between the two parties where each party will get an equal 40% yield.
Huntington’s disease (HD) belongs to protein misfolding disorders associated with polyglutamine (polyQ)-rich mutant huntingtin (mHtt) protein inclusions. Currently, it is indicated that the aggregation of polyQ-rich mHtt participates in neuronal toxicity and dysfunction. Here, we designed and synthesized a polyglutamine-specific gold nanoparticle (AuNP) complex, which specifically targeted mHtt and alleviated its toxicity. The polyglutamine-specific AuNPs were prepared by decorating the surface of AuNPs with an amphiphilic peptide (JLD1) consisting of both polyglutamine-binding sequences and negatively charged sequences. By applying the polyQ aggregation model system, we demonstrated that AuNPs–JLD1 dissociated the fibrillary aggregates from the polyQ peptide and reduced its β-sheet content in a concentration-dependent manner. By further integrating polyethyleneimine (PEI) onto AuNPs–JLD1, we generated a complex (AuNPs–JLD1–PEI). We showed that this complex could penetrate cells, bind to cytosolic mHtt proteins, dissociate mHtt inclusions, reduce mHtt oligomers, and ameliorate mHtt-induced toxicity. AuNPs–JLD1–PEI was also able to be transported to the brain and improved the functional deterioration in the HD Drosophila larva model. Our results revealed the feasibility of combining AuNPs, JLD1s, and cell-penetrating polymers against mHtt protein aggregation and oligomerization, which hinted on the early therapeutic strategies against HD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.