A joint team of researcher Xiaoling Gao from the Department of Pharmacology and Chemical Biology, School of Basic Medical Sciences, Shanghai Jiao Tong University and Professor Hongzhuan Chen from Shanghai University of Traditional Chinese Medicine has constructed a multifunctional lipoprotein mimetic nanostructure RAP-RL remodeling neurovascular unit (NVU) for the early pathological events of cerebrovascular dysfunction in Alzheimer's disease (AD), which can effectively reverse the spatial learning and memory deficits in AD model mice, providing It provides new targets and ideas for Alzheimer's disease intervention. The paper was recently published in Advanced Science.
The neurovascular unit is composed of neurons-glial cells-vessels and is an important structure for maintaining the stability of the brain microenvironment. Neurovascular unit lesions are closely related to the pathogenesis of Alzheimer's disease. If the structural and functional integrity of the neurovascular unit is compromised, the energy supply and the homeostasis of the brain microenvironment will be altered, thus affecting the pathophysiological process and cognitive function of Alzheimer's disease.
In this study, we developed a multifunctional integrated lipoprotein bionanostructure, RAP-RL, to address the different aspects of neurovascular unit lesions and the pathogenesis of Alzheimer's disease, integrating RAP, a peptide that recognizes late glycosylated receptors highly expressed on cerebrovascular endothelial cells damaged by Alzheimer's disease, GM1, a neuroprotective lipid, and ApoE3, a lipoprotein that promotes β-amyloid clearance and anti-inflammatory functions in the brain.
The experimental results showed that intravenous administration of RAP-RL could effectively act on the injured brain microvasculature, improve cerebral blood flow, and significantly reverse the spatial learning and memory impairment in transgenic APP/PS1 mice with Alzheimer's disease. This study provides a new proof of concept for remodeling neurovascular units and improving cognition.
SciTech Pharma is pursuing opportunities in this important category involving CNS. Using our proprietary SigmaHit program, we are seeking to find solutions in an innovative way, to meet the challenges that these diseases have posed to the pharmaceutical industry for such a long time.
