A VEGF Fragment Encompassing Residues 10-30 Inhibits Aβ1-42 Amyloid Aggregation and Exhibits Neuroprotective Properties Matching the Full-Length Protein.

IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Stefania Zimbone, M Laura Giuffrida, Michele F M Sciacca, Rita Carrotta, Fabio Librizzi, Danilo Milardi, Giulia Grasso
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引用次数: 0

Abstract

The intricate relationship between brain vascular diseases and neurodegeneration has garnered increased attention in the scientific community. With an aging population, the incidence of these two conditions is likely to increase, making it imperative to understand the underlying common molecular mechanisms and unveiling novel avenues for therapy. Prompted by the observation that Aβ peptide aggregation has been implicated in the development of cerebral amyloid angiopathy (CAA) and that elevated concentrations of vascular endothelial growth factor (VEGF) in the cerebrospinal fluid (CSF) have been correlated with less cognitive decline in Alzheimer's disease (AD), we demonstrate that a small peptide (Pep9) encompassing the 10-30 sequence of VEGF exhibits significant ability to inhibit the aggregation of the Aβ1-42 peptide, as well as the formation of toxic oligomers. AFM studies confirmed this inhibitory capacity, which is also paralleled by a significant reduction of the random coil to a beta-sheet conformational transition. Further studies have shown that Pep9 protects differentiated neuroblastoma SH-SY5Y cells from Aβ toxicity, being even more effective than full-length protein in preventing amyloid-induced neuronal death. The use of a control peptide wherein two histidines are substituted with glycines (H11G and H12G) suggests a close relationship between the peptide amino acid sequence and its antiaggregating/neuroprotective activity. Overall, this study provides insight into the role of VEGF in AD and suggests that specific VEGF fragments could be beneficial in the treatment of this condition.

包含 10-30 位残基的血管内皮生长因子片段可抑制 Aβ1-42 淀粉样蛋白聚集,并表现出与全长蛋白相匹配的神经保护特性。
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来源期刊
ACS Chemical Neuroscience
ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL
CiteScore
9.20
自引率
4.00%
发文量
323
审稿时长
1 months
期刊介绍: ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research
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