Review
Chemistry, Multidisciplinary
Jianglong Kong, Runxuan Chu, Yi Wang
Summary: Stroke is a major cause of death and disability worldwide. Neuroprotective therapy, combined with thrombolytic therapy, is an important treatment for stroke.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Jose David Sanchez-Martinez, Monica Bueno, Gerardo Alvarez-Rivera, Jose Tudela, Elena Ibanez, Alejandro Cifuentes
Summary: Orange by-products are a rich source of health-promoting compounds like terpenes, with ethyl acetate extract showing the most promising neuroprotective and antioxidant activities. The study used bioactivity assays and phytochemical profiling to determine the content and activity of beneficial compounds in orange juice by-products. Hydrocarbons mono- and sesquiterpenoids were found to have high potential to cross the blood-brain barrier in vitro.
Review
Biochemistry & Molecular Biology
Jacob Raber, Elizabeth M. M. Rhea, William A. A. Banks
Summary: In this review manuscript, the effects of common viruses such as HIV, herpes, hepatitis, influenza, RSV, and SARS-CoV-2 on insulin sensitivity and blood-brain barrier (BBB) function are discussed, along with the underlying mechanisms. These viruses have different abilities to cross the BBB, disrupt it, and alter its function. Additionally, the risk of infection and development of diabetes is increased by certain viruses, while enhanced TNF-a levels play a role in the detrimental effects of HIV and hepatitis. The combined viral exposures of influenza, RSV, and COVID-19 are of concern and further research is needed to understand their effects on insulin sensitivity and BBB function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Yury Maritza Zapata Lopera, Gabriela Trejo-Tapia, Manases Gonzalez-Cortazar, Maribel Herrera-Ruiz, Alejandro Zamilpa, Enrique Jimenez-Ferrer
Summary: This study evaluated the protective effects of Bouvardia ternifolia root extracts on the blood-brain barrier and the positive regulation of cytokines IL-1β, IL-6, and TNF-α, and characterized the compounds present in the dichloromethane (BtD) and hexane (BtH) extracts. The results showed that BtH and BtD extracts significantly reduced LPS-induced blood-brain barrier leakage and modulated the production of cytokines. This research provides important insights into the pharmacological effects of Bouvardia ternifolia.
Article
Biochemistry & Molecular Biology
Adam Juhasz, Ditta Ungor, Norbert Varga, Gabor Katona, Gyorgy T. Balogh, Edit Csapo
Summary: The encapsulation possibilities of neuroprotective drug KYNA using lipid-based nanocarriers to increase BBB permeability were studied. Preparation conditions and characterization of liposomes were optimized. The drug-loaded liposomes showed improved BBB penetration and lipid membrane retention compared to the unformatted drug.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Hairong Zhao, Mei Wang, Xi Huang, Xiumei Wu, Huai Xiao, Fanmao Jin, Jiaming Lv, Jidong Cheng, Yu Zhao, Chenggui Zhang
Summary: Wasp venom exhibits potential neuroprotective effects on acute ischaemic stroke (AIS) in rats, improving neurological impairment, promoting blood flow recovery, reducing infarct volume, and regulating blood-brain barrier permeability. The venom also inhibits inflammation and apoptosis, and modulates angiogenesis factors in the brain.
PHARMACEUTICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vinod Kumar, John D. Lee, Elizabeth J. Coulson, Trent M. Woodruff
Summary: The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) are specialized structures that limit molecule entry and maintain homeostasis within the central nervous system. This study developed and validated a quantitative method for assessing BBB and BSCB integrity using sodium fluorescein. The method revealed changes in permeability in models of neurodegenerative diseases and could contribute to understanding the role of these neuroprotective barriers in neurodegeneration processes.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Clinical Neurology
Manon Leclerc, Philippe Bourassa, Cyntia Tremblay, Vicky Caron, Camille Sugere, Vincent Emond, David A. Bennett, Frederic Calon
Summary: This study reveals that impairment of insulin receptors at the blood-brain barrier contributes to brain insulin resistance in Alzheimer's disease, in association with beta-amyloid pathology, based on experiments with human brain samples and animal models.
Review
Nutrition & Dietetics
Amanda Lo Van, Nathalie Bernoud-Hubac, Michel Lagarde
Summary: DHA-LysoPC and AceDoPC are proposed as the main transporters of DHA to the brain. Esterification of DHA within these compounds can enhance their neuroprotective effects, with AceDoPC also possessing antioxidant properties and the ability to generate acetylcholine.
Article
Biochemistry & Molecular Biology
Alexy Tran-Dinh, Angelique Levoye, David Couret, Lauriane Galle-Treger, Martine Moreau, Sandrine Delbosc, Camille Hoteit, Philippe Montravers, Pierre Amarenco, Thierry Huby, Olivier Meilhac
Summary: Research shows that high-density lipoproteins (HDL) have neuroprotective effects in acute ischemic stroke, with the HDL receptor SR-BI expressed by endothelial cells playing a key role. HDL therapy limits infarct volume and blood-brain barrier leakage, while maintaining the integrity of the blood-brain barrier.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Applied
Lipeng Wu, Weisu Huang, Kejie Peng, Yixuan Wang, Qi Chen, Baiyi Lu
Summary: In this study, verbascoside (VER) was encapsulated into lipid nanocapsules (LNC) by reverse micelle (RM) to improve its stability. Menthol was used as an envoy drug to enhance its permeability across the blood-brain barrier (BBB) and neuroprotective activity.
Article
Cell Biology
Yijie Yang, Ning Wang, Li Xu, Yixin Liu, Lulu Huang, Mengyang Gu, Yue Wu, Wenyi Guo, Hao Sun
Summary: Glaucoma is a leading cause of irreversible blindness, characterized by progressive retinal neurodegeneration and local inflammation. This study explores the involvement of aryl hydrocarbon receptor (AhR) and its agonists tryptophan metabolites in glaucoma development. Findings suggest altered serum tryptophan metabolism and reduced retinal AhR expression in glaucoma patients. Additionally, a tryptophan metabolite called ITE can down-regulate retinal inflammation and protect retinal ganglion cells from ischemia/reperfusion injury through AhR activation. The study identifies a potential mechanism involving the limitation of microglial inflammation through ITE. These findings provide new insights for glaucoma treatment by targeting the disrupted AhR signaling resulting from disturbed tryptophan metabolism.
CELL DEATH & DISEASE
(2023)
Review
Clinical Neurology
Mackenzie M. Aychman, David L. Goldman, Joshua S. Kaplan
Summary: Cannabidiol (CBD) has potential therapeutic effects against the secondary injury cascade from traumatic brain injury (TBI) by initiating anti-inflammatory, antioxidative, and antiepileptic properties. The lack of effective broad treatment strategies for TBI highlights the importance of CBD's mechanistic support in countering the damaging mechanisms and providing neuroprotective benefits. Future clinical research and ongoing clinical trials are necessary to further examine CBD's efficacy in TBI treatment protocols.
FRONTIERS IN NEUROLOGY
(2023)
Review
Pharmacology & Pharmacy
Yijun Hu, Hong Zhou, Huanxin Zhang, Yunlong Sui, Zhen Zhang, Yuntao Zou, Kunquan Li, Yunyi Zhao, Jiangbo Xie, Lunzhong Zhang
Summary: This article summarizes the neuroprotective effects of Dexmedetomidine in various models of neurological damage and examines its mechanisms including inhibition of inflammatory reactions, reduction of apoptosis and autophagy, and protection of the blood-brain barrier and enhancement of stable cell structures.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna D. Grabowska, Mateusz Watroba, Joanna Witkowska, Agnieszka Mikulska, Nuno Sepulveda, Dariusz Szukiewicz
Summary: The blood-brain barrier (BBB) plays a crucial role in regulating the flow of substances between the blood and the central nervous system. Disruption of the BBB due to imbalanced blood glucose levels can lead to neuroinflammation and increase the risk of neurodegenerative diseases. Resveratrol (RSV), a natural compound with anti-diabetic, anti-inflammatory, and neuroprotective properties, activates SIRT1, a key regulator of metabolism. This study aimed to assess the response of astrocyte SIRT1 to neuroinflammation and RSV treatment in different glycemic backgrounds. The results showed that abnormal glycemic states had a worse prognosis for RSV therapy effectiveness compared to normoglycemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dai Hatakeyama, Masaki Shoji, Seiryo Ogata, Takeshi Masuda, Masahiro Nakano, Tsugunori Komatsu, Ayaka Saitoh, Kyoko Makiyama, Hazuki Tsuneishi, Asuka Miyatake, Mizuki Takahira, Erina Nishikawa, Ayana Ohkubo, Takeshi Noda, Yoshihiro Kawaoka, Sumio Ohtsuki, Takashi Kuzuhara
Summary: The PA subunit of influenza A virus RNA-dependent RNA polymerase undergoes acetylation by histone acetyltransferases, which accelerates its endonuclease activity. Specifically, the lysine residue at position 19 in the PA subunit is identified as a target for acetylation, enhancing the endonuclease activity of the virus.
Article
Chemistry, Medicinal
Hinako Nagano, Seiryo Ogata, Shingo Ito, Takeshi Masuda, Sumio Ohtsuki
Summary: This study reveals the role of Podocalyxin (PODXL) in blood-brain barrier function. PODXL knockdown affects immune response and intracellular trafficking, and regulates the protein expression and efflux activity of ABCB1/MDR1.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Hinako Nagano, Shingo Ito, Takeshi Masuda, Sumio Ohtsuki
Summary: The study suggests that INSR-mediated signaling is involved in regulating the expression of functional proteins at the blood-brain barrier (BBB), contributing to BBB function maintenance. Changes in protein expressions, particularly those related to amyloid-beta peptides, in INSR knockdown cells may contribute to the development of cerebral amyloid angiopathy through the suppression of INSR-mediated signaling.
PHARMACEUTICAL RESEARCH
(2022)
Article
Oncology
Seiryo Ogata, Takeshi Masuda, Shingo Ito, Sumio Ohtsuki
Summary: Targeted proteomics is a method that quantifies target proteins using liquid chromatography-tandem mass spectrometry. It allows rapid development, simultaneous measurement of multiple proteins, and high-specificity detection of modifications. It can seamlessly transfer candidate cancer biomarker proteins from discovery to verification and validation, accelerating the cancer biomarker pipeline.
Article
Chemistry, Multidisciplinary
Kristiina M. Huttunen, Tetsuya Terasaki, Arto Urtti, Ahmed B. Montaser, Yasuo Uchida
Summary: One of the major challenges in CNS-drug development is the presence of barriers that prevent substances from entering the brain. This review discusses the expression profiles of transporters in these barriers and how they affect drug disposition in the brain. It also highlights the advancements in structural biology and computational resources that have improved our understanding of transporter dynamics and aided in the design of transporter-utilizing compounds.
PHARMACEUTICAL RESEARCH
(2022)
Article
Chemistry, Analytical
Takeshi Masuda, Yuma Inamori, Arisu Furukawa, Maki Yamahiro, Kazuki Momosaki, Chih-Hsiang Chang, Daiki Kobayashi, Hiroto Ohguchi, Yawara Kawano, Shingo Ito, Norie Araki, Shao-En Ong, Sumio Ohtsuki
Summary: This study presents a water droplet in-oil digestion (WinO) method for proteomic analysis in limited sample amounts. The method increases protein and peptide recovery by minimizing the contact area between the sample solution and the container. It has been successfully applied to single-cell proteomics and shows promise for its wide applicability and suitability.
ANALYTICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Keita Kitamura, Ayaka Okamoto, Hanae Morio, Ryuto Isogai, Ryo Ito, Yoshiyuki Yamaura, Saki Izumi, Takafumi Komori, Shingo Ito, Sumio Ohtsuki, Hidetaka Akita, Tomomi Furihata
Summary: This study characterizes the ability of the hiMCS-BBB models to evaluate receptor-mediated transcytosis (RMT)-mediated blood-brain barrier (BBB) penetration properties of middle/macromolecules. The results show that the hiMCS-BBB models have the potential to provide valuable tools for exploring and identifying middle/macromolecules with excellent BBB permeability levels.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Haruki Horiguchi, Tsuyoshi Kadomatsu, Shinsei Yumoto, Takeshi Masuda, Keishi Miyata, Shuji Yamamura, Michio Sato, Jun Morinaga, Sumio Ohtsuki, Hideo Baba, Toshiro Moroishi, Yuichi Oike
Summary: Tumor cell-derived ANGPTL2 promotes beta-catenin-driven intestinal tumorigenesis by upregulating OB-cadherin expression and blocking destruction complex-independent proteasomal degradation of beta-catenin proteins. It also leads to decreased cell surface integrin alpha 5 beta 1 expression.
Article
Pharmacology & Pharmacy
Toshiki Kurosawa, Yuma Tega, Yasuo Uchida, Kei Higuchi, Hidetsugu Tabata, Takaaki Sumiyoshi, Yoshiyuki Kubo, Tetsuya Terasaki, Yoshiharu Deguchi
Summary: The PICK method successfully identified TM7SF3 and LHFPL6 as candidate proteins for the H+/OC antiporter and their functional analysis confirmed their role as components of this antiporter.
Article
Chemistry, Multidisciplinary
Ayano Mori, Takeshi Masuda, Shingo Ito, Sumio Ohtsuki
Summary: This study comprehensively assessed the digestion efficiency and stability of tryptic peptides, identified optimal signature peptides for human hepatic transporters and membrane marker proteins, and provided reliable quantification of human hepatic transporters for integrated pharmacokinetic studies.
PHARMACEUTICAL RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Yuki Yamasaki, Takashi Moriwaki, Seiryo Ogata, Shingo Ito, Sumio Ohtsuki, Genki Minegishi, Satoshi Abe, Yumi Ohta, Kanako Kazuki, Kaoru Kobayashi, Yasuhiro Kazuki
Summary: This study developed a novel P-glycoprotein humanized mouse line carrying the 2677G>T mutation and evaluated its influence on the expression and function of P-glycoprotein at the blood-brain barrier. The results showed that the mutation did not alter the expression levels of P-glycoprotein but increased the brain penetration of P-glycoprotein substrates. This mutant mouse line provides a useful model for studying the impact of MDR1 gene mutations on P-glycoprotein at the blood-brain barrier.
PHARMACOGENETICS AND GENOMICS
(2022)
Article
Cell Biology
Takayuki Hoshii, Sarah Perlee, Sota Kikuchi, Bahityar Rahmutulla, Masaki Fukuyo, Takeshi Masuda, Sumio Ohtsuki, Tomoyoshi Soga, Behnam Nabet, Atsushi Kaneda
Summary: The protein degrader technology was used in this study to degrade SETD1A and investigate its role in acute myeloid leukemia (AML) cells. The results showed that SETD1A degradation led to downregulation of DNA repair and heme biosynthesis pathways, and SETD1A was also found to be essential for maintaining mitochondrial respiration in AML cells. Furthermore, the study revealed a non-enzymatic role of SETD1A in transcriptional pause release, providing insight into the mechanism of RNA polymerase II (RNAPII) pausing and its function in cancer.
Article
Cell Biology
Marie-Pierre Dehouck, Masanori Tachikawa, Yutaro Hoshi, Kotaro Omori, Claude-Alain Maurage, Guillaume Strecker, Lucie Dehouck, Marie-Christine Boucau, Yasuo Uchida, Fabien Gosselet, Tetsuya Terasaki, Yannis Karamanos
Summary: This study compared the protein expression levels of human brain-like endothelial cells (hBLECs) and human brain microvessels (hBMVs) using quantitative targeted absolute proteomics. The results showed that hBLECs had higher protein levels of CD144, CD147, MRP4, Annexin A6, and caveolin-1 compared to hBMVs, while the protein levels of MCT1, Connexin 43, TfR1, and claudin-5 were relatively lower. Furthermore, BCRP was found to be more expressed than MDR1 in hBLECs. These findings contribute to a better understanding of the characteristics of hBLECs and demonstrate the equivalence of in vitro BBB models with in vivo models in terms of transport properties.
Article
Pharmacology & Pharmacy
Seiryo Ogata, Shingo Ito, Takeshi Masuda, Sumio Ohtsuki
Summary: This study investigated the diurnal changes in protein expression in the blood-brain barrier (BBB) using quantitative proteomics. The results showed that protein expression related to transport function and physical barrier at the BBB remained stable throughout the day, while proteins involved in other biological processes exhibited diurnal variation.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Clinical Neurology
Yi Wang, Maki Sakaguchi, Hemragul Sabit, Sho Tamai, Toshiya Ichinose, Shingo Tanaka, Masashi Kinoshita, Yasuo Uchida, Sumio Ohtsuki, Mitsutoshi Nakada
Summary: COL1A2 is significantly upregulated in GBM patients compared with healthy controls and is associated with poor prognosis. Inhibition of COL1A2 suppresses GBM cell proliferation and invasion, likely through inducing cell cycle arrest. COL1A2 may be a promising therapeutic target for GBM treatment.
JOURNAL OF NEUROSURGERY
(2022)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)