Dongju Zhao , Fan Yang , Yining Liu , Meng Cheng , Ziyao Chen , Caihua Ye , Jin Chang , Yan Dou
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引用次数: 0
Abstract
Chronic neuromicrovascular dysfunction and its induced multifaceted neuropathology involving the interaction of cellular differential pathogenic mechanisms pose challenges to the precise treatment of Alzheimer’s disease (AD). Here we report the development of an ellagic acid-derived self-assembled micellar SIRT1 activator (REn) that enables cross-scale targeted remodeling of neurovascular and neurometabolic coupling in AD. Efficient transcytosis of the receptor for advanced glycation endproducts by modified peptides allows for programmed delivery of REn to cerebral microvessels and parenchymal neurons. The resulting SIRT1 cascade activation enhances endothelial nitric oxide signaling-mediated cerebral blood flow and the blood-brain barrier integrity, while promoting neuronal mitochondrial biogenesis and glucose metabolic patterns toward oxidative phosphorylation. This multipronged remodeling strategy achieves a cooperative normalization of brain energy supply and β-amyloid clearance in AD mice, showing profound improvement in cognitive impairment. This work provides an advanced pharmacological option for cross-scale targeted treatment of neurodegenerative diseases associated with neurovascular dysfunction.
期刊介绍:
Nano Today is a journal dedicated to publishing influential and innovative work in the field of nanoscience and technology. It covers a wide range of subject areas including biomaterials, materials chemistry, materials science, chemistry, bioengineering, biochemistry, genetics and molecular biology, engineering, and nanotechnology. The journal considers articles that inform readers about the latest research, breakthroughs, and topical issues in these fields. It provides comprehensive coverage through a mixture of peer-reviewed articles, research news, and information on key developments. Nano Today is abstracted and indexed in Science Citation Index, Ei Compendex, Embase, Scopus, and INSPEC.