Functional characterization of the brain-to-blood efflux clearance of human amyloid-β peptide (1–40) across the rat blood–brain barrier

2006 ◽  
Vol 56 (3) ◽  
pp. 246-252 ◽  
Author(s):  
Shingo Ito ◽  
Sumio Ohtsuki ◽  
Tetsuya Terasaki
2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Agnès Dodacki ◽  
Matthew Wortman ◽  
Bruno Saubaméa ◽  
Stéphanie Chasseigneaux ◽  
Sophie Nicolic ◽  
...  

2006 ◽  
Vol 2 ◽  
pp. S533-S534
Author(s):  
Kaoru Yamada ◽  
Chiori Yabuki ◽  
Masanori Tachikawa ◽  
Sumio Ohtsuki ◽  
Dudley K. Strickland ◽  
...  

RSC Advances ◽  
2019 ◽  
Vol 9 (25) ◽  
pp. 14126-14131 ◽  
Author(s):  
Jinzhuan Wang ◽  
Kun Wang ◽  
Zhenzhu Zhu ◽  
Yafeng He ◽  
Changli Zhang ◽  
...  

A BBB-passable nanoscale silica–cyclen chelator effectively reduces the metal-induced Aβ aggregates and related ROS, thereby decreasing the neurotoxicity of Aβ.


Physiology ◽  
2002 ◽  
Vol 17 (6) ◽  
pp. 231-234 ◽  
Author(s):  
Bruno Hagenbuch ◽  
Bo Gao ◽  
Peter. J. Meier

Distinct transport proteins regulate the movement of waste products and xenobiotics across the blood-brain barrier (BBB). Members of the drug transporter families MDR, MRP, and OATP have been identified in the BBB, and a detailed characterization of the involved proteins is now required to target drugs more efficiently to the brain.


2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Aarushi Sahni ◽  
Nicole Katchur

The Blood-Brain Barrier (BBB) is a highly selective filter responsible for allowing certain gases such as oxygen and lipid-soluble molecules to pass (Anand 2014). Its selectiveness makes it challenging for many therapeutics to combat Alzheimer’s and Parkinson’s disease with external drug therapies. Large-molecule drug therapies never pass the BBB while small-molecule drugs pass only about 5% of the time (Pardridge 2005). In Alzheimer’s disease, tight junctions between endothelial cells degrade, causing an unregulated accumulation of amyloid-β (Aβ) protein (Ramanathan 2015). Consequently, this leads to the formation of neurofibrillary tangles that cut off the nutrient supply to the brain cells and kill neurons (Ramanathan 2015). In Parkinson’s disease, astrocyte mutations cause a build-up of α-synuclein (αSyn) which affects the neuroinflammatory response and causes dysfunction in dopaminergic neurons (Booth 2017; Meade 2019). New drug therapies for Alzheimer’s and Parkinson’s continue to undergo trials; some such as FPS-ZM1 and tilavonemab for Alzheimer’s and Ravicti for Parkinson’s have shown promising results. In addition, similarities in dysfunction for both diseases and some types of cancer have sparked possibilities in retargeting cancer drugs to improve Alzheimer's and Parkinson’s pathologies. This review will summarize current therapeutic advancements for Alzheimer’s and Parkinson’s disease and their possible future contributions.


Membranes ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 212 ◽  
Author(s):  
Hernán Cortés ◽  
Sergio Alcalá-Alcalá ◽  
Isaac H. Caballero-Florán ◽  
Sergio A. Bernal-Chávez ◽  
Arturo Ávalos-Fuentes ◽  
...  

The blood-brain barrier (BBB) is a sophisticated and very selective dynamic interface composed of endothelial cells expressing enzymes, transport systems, and receptors that regulate the passage of nutrients, ions, oxygen, and other essential molecules to the brain, regulating its homeostasis. Moreover, the BBB performs a vital function in protecting the brain from pathogens and other dangerous agents in the blood circulation. Despite its crucial role, this barrier represents a difficult obstacle for the treatment of brain diseases because many therapeutic agents cannot cross it. Thus, different strategies based on nanoparticles have been explored in recent years. Concerning this, chitosan-decorated nanoparticles have demonstrated enormous potential for drug delivery across the BBB and treatment of Alzheimer’s disease, Parkinson’s disease, gliomas, cerebral ischemia, and schizophrenia. Our main objective was to highlight the high potential of chitosan adsorption to improve the penetrability through the BBB of nanoformulations for diseases of CNS. Therefore, we describe the BBB structure and function, as well as the routes of chitosan for crossing it. Moreover, we define the methods of decoration of nanoparticles with chitosan and provide numerous examples of their potential utilization in a variety of brain diseases. Lastly, we discuss future directions, mentioning the need for extensive characterization of proposed nanoformulations and clinical trials for evaluation of their efficacy.


2020 ◽  
Vol 21 (3) ◽  
pp. 934 ◽  
Author(s):  
Romain Versele ◽  
Mariangela Corsi ◽  
Andrea Fuso ◽  
Emmanuel Sevin ◽  
Rita Businaro ◽  
...  

Alzheimer’s disease (AD) is characterized by the abnormal accumulation of amyloid-β (Aβ) peptides in the brain. The pathological process has not yet been clarified, although dysfunctional transport of Aβ across the blood–brain barrier (BBB) appears to be integral to disease development. At present, no effective therapeutic treatment against AD exists, and the adoption of a ketogenic diet (KD) or ketone body (KB) supplements have been investigated as potential new therapeutic approaches. Despite experimental evidence supporting the hypothesis that KBs reduce the Aβ load in the AD brain, little information is available about the effect of KBs on BBB and their effect on Aβ transport. Therefore, we used a human in vitro BBB model, brain-like endothelial cells (BLECs), to investigate the effect of KBs on the BBB and on Aβ transport. Our results show that KBs do not modify BBB integrity and do not cause toxicity to BLECs. Furthermore, the presence of KBs in the culture media was combined with higher MCT1 and GLUT1 protein levels in BLECs. In addition, KBs significantly enhanced the protein levels of LRP1, P-gp, and PICALM, described to be involved in Aβ clearance. Finally, the combined use of KBs promotes Aβ efflux across the BBB. Inhibition experiments demonstrated the involvement of LRP1 and P-gp in the efflux. This work provides evidence that KBs promote Aβ clearance from the brain to blood in addition to exciting perspectives for studying the use of KBs in therapeutic approaches.


2006 ◽  
Vol 14 (7S_Part_5) ◽  
pp. P298-P299
Author(s):  
Kerry Rennie ◽  
Trevor Atkinson ◽  
Leslie Brown ◽  
Michel Menard ◽  
Eric Brunette ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document