Amyloid oligomers and protofibrils increase cell membrane permeability, eventually leading to cell death. Here, we demonstrate that amyloid oligomer toxicity and membrane permeabilization can be reversed using the membrane sealant copolymer poloxamer 188. The data indicate that amyloid oligomer toxicity is caused by defects in the lipid bilayer of the type that are sealed by poloxamer 188. Our results also suggest the possibility of using polymer-based membrane sealants to prevent or reverse amyloid oligomer toxicity in vivo. Because the ability to permeabilize membranes is a generic property of amyloid oligomers, this therapeutic approach may be effective for the treatment of many degenerative diseases caused in part by the interaction of misfolded proteins with cell membranes, as in Alzheimer's disease, type II diabetes, and a host of others.
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http://dx.doi.org/10.1016/j.jmb.2009.06.024 | DOI Listing |
J Pharm Anal
December 2024
MTA-HUN-REN TTK Lendület "Momentum" Peptide-Based Vaccines Research Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Budapest, H-1117, Hungary.
The aim of the research is to increase the applicability of lipopeptides as drugs. To this end, non-ionic triblock copolymers, namely poloxamers, were applied. The physico-chemical properties of poloxamers vary depending on the length of the blocks.
View Article and Find Full Text PDFAAPS J
January 2025
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Protein aggregates and particles in biopharmaceuticals can induce adverse immune responses in patients. Thus, suppression of the formation of protein aggregates and particles is important for the successful development of therapeutic proteins. Mechanical stresses, including agitation, are widely recognized as stress factors that generate protein aggregates and particles.
View Article and Find Full Text PDFSci Rep
January 2025
Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Mitochondrial transplantation (MTx) offers a promising therapeutic approach to mitigate mitochondrial dysfunction in conditions such as ischemia-reperfusion (IR) injury. The quality and viability of donor mitochondria are critical to MTx success, necessitating the optimization of isolation protocols. This study aimed to assess a rapid mitochondrial isolation method, examine the relationship between mitochondrial size and membrane potential, and evaluate the potential benefits of Poloxamer 188 (P-188) in improving mitochondrial quality during the isolation process.
View Article and Find Full Text PDFInt J Pharm
January 2025
Department of Chemical Sciences, Bernal Institute, University of Limerick, Ireland; SSPC Science Foundation Ireland Research Centre for Pharmaceuticals, University of Limerick, Ireland. Electronic address:
The potent pro-inflammatory cytokine, interferon gamma (IFN-γ), is an enticing therapeutic target because of its accelerator role in several acute and chronic inflammatory processes. In this work, poloxamer 407 is developed as an in-situ gelling polymer for a long-acting formulation to deliver a serine protease, C5a peptidase (ScpA) from Streptococcus pyogenes. ScpA is well known for its activity against the complement factor C5a but has also recently been shown to cleave IFN-γ in vitro into inactive fragments.
View Article and Find Full Text PDFInt J Pharm
January 2025
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 51006 China. Electronic address:
Androgenic alopecia (AGA), the most prevalent type of progressive hair loss, currently lacks an effective topical treatment regimen. In this study, we synthesized an ionic liquid (IL) to co-solubilize minoxidil (MXD) and finasteride (FIN) and subsequently formulated them into an in situ thermosensitive ionic liquid/cyclodextrin/poloxamer hydrogel (ICPG), termed M + F@ICPG. M + F@ICPG was developed for the transdermal co-delivery of these two drugs, aiming to provide a multipath therapeutic approach for AGA while avoiding the adverse effects commonly associated with oral FIN and topical MXD tincture.
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