CPNQ is a promoter of polyQ and α-synuclein inclusion formation and rescuer of Htt proteosomal dysfunction and α-synuclein toxicity.
Misfolded proteins accumulate in many neurodegenerative diseases, including huntingtin in Huntington′s disease and alpha-synuclein in Parkinson′s disease. The disease-causing proteins can take various conformations and are prone to aggregate and form larger cytoplasmic or nuclear inclusions. CPNQ (B2) was identified as a compound that promotes inclusion formation in cellular models of both Huntington′s disease and Parkinson′s disease. Despite the aggregate-forming specifics the compound prevents huntingtin-mediated proteasome dysfunction and reduces alpha-synuclein-mediated toxicity. These results demonstrate that compounds that increase inclusion formation may actually lessen cellular pathology in both Huntington′s and Parkinson′s diseases, suggesting a therapeutic approach for neurodegenerative diseases caused by protein misfolding. The ability of B2 to prevent toxicity, despite increasing inclusions, suggests that inclusions are beneficial rather than toxic, which will be further explored as the molecular target and mechanism. CPNQ (B2) is a desirable tool for both Huntington′s and Parkinson′s research.
The Journal of infection, 82(2), 207-215 (2021-01-17)
Polymyxin B is a last-line antibiotic for multidrug-resistant gram-negative bacterial infections. However, limited safety and pharmacokinetic information is available. We investigated the safety and pharmacokinetics of intravenous polymyxin B in healthy subjects. An open-label, single-dose clinical trial was conducted in
The opportunistic human pathogen Pseudomonas aeruginosa can thrive under microaerophilic to anaerobic conditions in the lungs of cystic fibrosis patients. RNASeq based comparative RNA profiling of the clinical isolate PA14 cultured in synthetic cystic fibrosis medium was performed after planktonic
Discovering the evolution of a tumor may help identify driver mutations and provide a more comprehensive view on the history of the tumor. Recent studies have tackled this problem using multiple samples sequenced from a tumor, and due to clinical
Short interspersed nuclear elements (SINEs) are highly abundant, RNA polymerase III-transcribed noncoding retrotransposons that are silenced in somatic cells but activated during certain stresses including viral infection. How these induced SINE RNAs impact the host-pathogen interaction is unknown. Here we
International journal of antimicrobial agents, 52(3), 365-371 (2018-05-29)
A number of companies manufacture polymyxin B using United States Pharmacopeia (USP) metrics, rather than chemical composition, to report biological activity. Given that polymyxin B contains several different components, it is unknown whether pharmacokinetic and pharmacodynamic variability exists between the
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