期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 34, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2021.102376
关键词
Polypeptides; Polymer-drug conjugates; Alcohol-induced neuroinflammation; Curcuminoids; miRNA
An optimized and targeted polypeptide-based nanoconjugate of a curcuminoid shows potential in attenuating alcohol-induced neuroinflammation and protecting against neural damage.
Alcohol abuse induces the expression of inflammatory mediators by activating the immune receptors to trigger neuroinflammation and brain damage; however, therapies that reduce neuroimmune system activation may protect against alcohol's damaging effects. Curcuminoids possess anti-inflammatory properties but suffer from low bioavailability; therefore, we designed a new receptor-targeted biodegradable star-shaped crosslinked polypeptide polymer that bears propargylamine moieties and bisdemethoxycurcumin (StClPr-BDMC-ANG) as an enhanced anti-inflammatory therapeutic that penetrates the blood-brain-barrier and ameliorates alcohol-induced neuroinflammation. StClPr-BDMC-ANG administration maintains the viability of primary glia and inhibits the ethanol-induced upregulation of crucial inflammatory mediators in the prefrontal and medial cortex in a mouse model of chronic ethanol consumption. StClPr-BDMC-ANG treatment also suppresses the ethanol-mediated downregulation of microRNAs known to negatively modulate neuroinflammation in the brain cortex (miRs 146a-5p and let-7b-5p). In summary, our results demonstrate the attenuation of alcohol-induced neuroinflammation by an optimized and targeted polypeptide-based nanoconjugate of a curcuminoid. (C) 2021 Elsevier Inc. All rights reserved.
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