Since it was discovered and its brain-protective role characterized, the blood-brain barrier (BBB), through the permeability-restricting action of the brain capillary endothelial cells, has been representing a hurdle for 95% of new medical compounds targeting the central nervous system. Recently, a BBB dysfunction is being found in an increasing number of pathologies such as brain ischaemic stroke, whose only therapy consists in a pharmacological thrombolysis limited to a small percentage of the admitted patients, because of the toxical effects of thrombolytics. And since the clinical failure of promising neuroprotectants, numerous studies of brain ischaemia were carried out, with physiopathological or pharmacological approaches refocused on the BBB, whose structural complexity is now expanded to perivascular cells, all forming a functional unit named the neurovascular unit (NVU). Nevertheless, in spite of the numerous molecular mechanisms identified, the process of BBB dysfunction in the ischaemia/reperfusion cascade remains insufficiently established to explain the pleiotropic action exerted by new pharmacological compounds, possibly protecting the entire NVU and representing potential treatments.
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http://dx.doi.org/10.1051/jbio/2012020 | DOI Listing |
J Control Release
January 2025
School of Medicine, Chongqing University, 131 Yubei Street, Shapingba District, Chongqing 400044, China. Electronic address:
Aging is a critical factor in the onset and progression of neurodegenerative diseases and cognitive decline, with aging-related neuroinflammation and cellular senescence being major contributors. In the aging brain, the cerebral vascular endothelium overexpresses vascular cell adhesion molecule 1 (VCAM1), activating microglia and leading to neuroinflammation and cognitive impairment. Quercetin, a natural neuroprotective agent widely used for treating neurodegenerative diseases, their therapeutic efficacy, however, is limited by its poor water solubility and inability to penetrate the blood-brain barrier (BBB).
View Article and Find Full Text PDFJ Control Release
January 2025
Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, 430074 Wuhan, PR China; Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, PR China; Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, 430071 Wuhan, PR China; Key Laboratory of Quality Control Technology for Virus-Based Therapeutics, Guangdong Provincial Medical Products Administration, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, PR China; University of Chinese Academy of Sciences, 100049 Beijing, PR China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031 Shanghai, PR China. Electronic address:
The blood-brain barrier (BBB) is a formidable barrier that restricts the entry of substances into the brain, complicating the study of brain function and the treatment of neurological conditions. Traditional methods of delivering genes from the periphery to the central nervous system (CNS) using adeno-associated viruses (AAVs) often require high doses, which can trigger immune responses and hepatotoxicity. Here, we developed a new AAV variant named AAVhu.
View Article and Find Full Text PDFBioorg Chem
January 2025
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentyev Avenue 9, Novosibirsk 630090, Russia. Electronic address:
Eudesmane-type sesquiterpene lactone isoalantolactone 1 is of great interest due to its availability, biological activity and synthetic application. Respective series of original spirocyclic (11S,5') (1,2,3-triazoline-eudesma-4,15-enolides) and (11S)-aziridine-eudesma-4,15-enolides were efficiently synthesized via a chemoselective 1,3-dipolar cycloaddition reaction of organic azides to the exocyclic double bond of the lactone ring of isoalantolactone or 13E-(aryl)isoalantolactones by heating in DMF or toluene. The thermal reactions of isoalantolactone with benzyl azide, 2-azidoethanol, or n-butyl azide in 2-methoxyethanol afforded 13-(alkyamino)isoalantolactones formed as a mixture of (Z) and (E)-isomers.
View Article and Find Full Text PDFBioorg Chem
January 2025
Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Central University of Punjab, Bathinda, India, 151401. Electronic address:
The pathology of Alzheimer's disease (AD) is complex due to its multifactorial nature and single targeting drugs proved inefficient. A series of novel 4-N-substituted-2-phenylquinazoline derivatives was designed and synthesized as potential multi-target directed ligands (MTDLs) through dual inhibition of AChE and MAO-B enzymes along with Aβ aggregation inhibition for the treatment of AD. Two compounds in the series, VAV-8 and VAV-19 were found to be the most potent inhibitors of both AChE and MAO-B enzymes and moderate inhibitor of Aβ, with good thermodynamic stability at the binding pocket of the enzymes.
View Article and Find Full Text PDFNeurobiol Aging
January 2025
Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
An emerging biomarker of blood-brain barrier (BBB) permeability is the time of exchange (Tex) of water from the blood to tissue, as measured by multi-echo arterial spin labeling (ASL) MRI. This new non-invasive sequence, already tested in mice, has recently been adapted to humans and optimized for clinical scanning time. In this study, we studied the normal variability of Tex over age and sex, which needs to be established as a reference for studying changes in neurological disease.
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