Article
Neurosciences
Nana Jin, Jianlan Gu, Ruozhen Wu, Dandan Chu, Yunn Chyn Tung, Jerzy Wegiel, Thomas Wisniewski, Cheng-Xin Gong, Khalid Iqbal, Fei Liu
Summary: This research discovered tau seeding activity in the brains of individuals with Down syndrome and found that higher tau seeding activity was associated with tau hyperphosphorylation. These findings provide insights into the progression of Alzheimer's disease and related disorders.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Jing Lu, Feng Liang, Ping Bai, Chenghao Liu, Miao Xu, Zhengwang Sun, Wenjie Tian, Yuanlin Dong, Yiying Zhang, Qimin Quan, Ashok Khatri, Yuan Shen, Edward Marcantonio, Gregory Crosby, Deborah J. Culley, Changning Wang, Guang Yang, Zhongcong Xie
Summary: Blood phosphorylated tau at threonine 217 (tau-PT217) is a biomarker for Alzheimer's disease and postoperative delirium. Anesthesia/surgery induced acute increases in blood tau-PT217 via enhanced generation in the lungs and release from B cells. Tau-PT217 might cross the blood-brain barrier, increasing neuronal excitability and inducing delirium-like behavior. Targeting B cells or mitochondrial function may have therapeutic potential for preventing or treating these conditions.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biophysics
Tushar Dubey, Shweta Kishor Sonawane, M. K. Chaitanya Mannava, Ashwini K. Nangia, Madhura Chandrashekar, Subashchandrabose Chinnathambi
Summary: Tau is a natively unfolded microtubule-associated protein and its post-translational modifications, especially phosphorylation, play a crucial role in the pathogenesis of Alzheimer's disease. Curcumin and Cur-Art co-amorphous were found to effectively inhibit Tau aggregation and restore impaired nuclear transport, suggesting their therapeutic potential against Tau protein in Alzheimer's disease.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Editorial Material
Oncology
Natividad R. Fuentes, Cullen M. Taniguchi
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma that restricts blood perfusion and nutrient delivery, creating a hypoxic microenvironment. Cancer-associated fibroblasts (CAF) are the main cellular components and producers of stroma in PDAC. This study investigates the role of hypoxia and hypoxia-inducible factor-1a (HIF1a) in maintaining fibroblast heterogeneity and promoting tumor progression in PDAC.
Article
Biochemistry & Molecular Biology
Ana Galesic, Ananya Rakshit, Giuliano Cutolo, Ricardo Palos Pacheco, Aaron T. Balana, Stuart P. Moon, Matthew R. Pratt
Summary: The study revealed that different sugars have varying effects on inhibiting amyloid formation, despite their structures having only small differences. This suggests the need for further investigation into the exact mechanism of amyloid inhibition by O-GlcNAc.
ACS CHEMICAL BIOLOGY
(2021)
Article
Clinical Neurology
Antonio Valencia, Veronica L. Reinhart Bieber, Bekim Bajrami, Galina Marsh, Stefan Hamann, Ru Wei, Karen Ling, Frank Rigo, H. Moore Arnold, Olga Golonzhka, Heike Hering
Summary: Acetylation of tau protein is dysregulated in Alzheimer's Disease. Despite knocking down HDAC6 protein, there was no observed increase in tau acetylation or changes in tau phosphorylation or aggregation in PS19 mice, indicating that HDAC6 does not impact tau pathology in this model.
FRONTIERS IN NEUROLOGY
(2021)
Article
Plant Sciences
Ningyi Zhang, Jochem B. Evers, Niels P. R. Anten, Leo F. M. Marcelis
Summary: Plants growing in dense stands receive light signals of varying strength from all directions, including from below. How plants perceive, integrate, and respond to light signals from below is a major question that needs to be addressed to better understand light-mediated plant interactions in different ecological and agricultural settings.
PLANT CELL AND ENVIRONMENT
(2021)
Article
Biochemistry & Molecular Biology
Amanda Schneeweis, Daniel T. S. Pak
Summary: Tau protein has been found to localize in various subcellular domains of neurons and has multiple physiological functions. However, the lack of comprehensive phosphosite analysis obscures our understanding of these functions. Therefore, establishing a comprehensive map of tau phosphorylation signatures can clarify its diverse physiological functions in different locations and guide the development of novel therapeutic strategies.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2023)
Article
Environmental Sciences
Jing Li, Junxiang Wang, Yuan-Liang Wang, Zhousong Luo, Chunyan Zheng, Guangxia Yu, Siying Wu, Fuli Zheng, Huangyuan Li
Summary: Cobalt nanoparticles (CoNPs) induce neurotoxicity by activating NOX2, resulting in ROS production, Tau protein phosphorylation, and inflammation in the brain.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Clinical Neurology
Jean-Pierre Bellier, Yuqi Cai, Sarah M. Alam, Thorsten Wiederhold, Arica Aiello, Jonathan S. Vogelgsang, Sabina Berretta, Jasmeer P. Chhatwal, Dennis J. Selkoe, Lei Liu
Summary: A wide array of post-translational modifications of the tau protein occurs in Alzheimer's disease (AD) and they are critical to pathogenesis and biomarker development. Several promising tau markers, pT181, pT217, and pT231, rely on increased phosphorylation within a common molecular motif threonine-proline-proline (TPP). The regional variability of pTPP tau suggests that examining different phosphorylation sites is essential for a comprehensive assessment of tau pathology.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Longfei Li, Jin Miao, Yanli Jiang, Chun-Ling Dai, Khalid Iqbal, Fei Liu, Dandan Chu
Summary: Tau immunotherapy, specifically targeting the microtubule-binding domain, shows promise in reducing tau pathology and improving cognitive function in Alzheimer's disease. In vitro and in vivo studies demonstrate that antibody 77G7 effectively clears tau and reduces tau hyperphosphorylation, offering a novel therapeutic opportunity for AD and related tauopathies.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Cell Biology
M. Bell-Simons, S. Buchholz, J. Klimek, H. Zempel
Summary: This study used a laser-based axotomy model combined with confocal microscopy to investigate the distribution of Tau protein in axons and its relationship with protein transport. The results suggest that axonal damage does not lead to the accumulation of Tau protein in the cell body or an increase in AT8 Tau phosphorylation.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Muhammad Farhan Khalid, Kanzal Iman, Amna Ghafoor, Mujtaba Saboor, Ahsan Ali, Urwa Muaz, Abdul Rehman Basharat, Taha Tahir, Muhammad Abubakar, Momina Amer Akhter, Waqar Nabi, Wim Vanderbauwhede, Fayyaz Ahmad, Bilal Wajid, Safee Ullah Chaudhary
Summary: PERCEPTRON is a high-performance TDP search tool that achieves high-throughput performance by executing optimized code on GPUs in parallel. Its intuitive graphical web interface allows users to set search parameters and visualize results. Validated results demonstrate that PERCEPTRON outperforms other tools by up to 135% in reported proteins and 10-fold in runtime.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Clinical Neurology
Binita Rajbanshi, Anuj Guruacharya, James W. Mandell, George S. Bloom
Summary: Tau phosphorylation at T217 increases as Alzheimer's disease progresses and is associated with diseased neurons. Extracellular tau oligomers can induce an increase in tau(pT217). Phosphorylation reduces tau's affinity for microtubules.
ALZHEIMERS & DEMENTIA
(2023)
Review
Immunology
Yijun Chen, Yang Yu
Summary: Alzheimer's Disease (AD) is mostly responsible for dementia, characterized by neuritic plaques and neurofibrillary tangles containing aggregated β-amyloid (Aβ) and hyperphosphorylated tau protein. Recent focus has been on disease-modifying therapy targeting Aβ, although the efficacy and long-term safety of such drugs are still controversial. Tau has gained attention as a therapeutic target due to its association with cognitive dysfunction. Inflammation, especially neuroinflammation, is linked to AD and tau pathology. Understanding the relationship between tau pathology and neuroinflammation will contribute to discovering therapeutic targets for AD and other tau-related diseases.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biochemistry & Molecular Biology
Abigail L. Emtage, Shailesh N. Mistry, Peter M. Fischer, Barrie Kellam, Charles A. Laughton
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2017)
Review
Chemistry, Medicinal
Gudrun A. Fridgeirsdottir, Robert Harris, Peter M. Fischer, Clive J. Roberts
JOURNAL OF PHARMACEUTICAL SCIENCES
(2016)
Correction
Chemistry, Medicinal
Katarzyna Nurzynska, Rupert P. Austin, Peter M. Fischer, Jonathan Booth, Frank Gommer
JOURNAL OF PHARMACEUTICAL SCIENCES
(2016)
Article
Chemistry, Medicinal
Peter M. Fischer
MEDICINAL RESEARCH REVIEWS
(2017)
Article
Pharmacology & Pharmacy
Jong Bong Lee, Atheer Zgair, Dhiaa A. Taha, Xiaowei Zang, Leonid Kagan, Tae Hwan Kim, Min Gi Kim, Hwi-yeol Yun, Peter M. Fischer, Pavel Gershkovich
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2017)
Article
Biochemical Research Methods
Jong Bong Lee, Atheer Zgair, Tae Hwan Kim, Min Gi Kim, Sun Dong Yoo, Peter M. Fischer, Pavel Gershkovich
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2017)
Article
Chemistry, Medicinal
Peter M. Fischer
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biology
Ana Crespillo-Casado, Joseph E. Chambers, Peter M. Fischer, Stefan J. Marciniak, David Ron
Article
Medicine, Research & Experimental
Gudrun A. Fridgeirsdottir, Robert J. Harris, Ian L. Dryden, Peter M. Fischer, Clive J. Roberts
MOLECULAR PHARMACEUTICS
(2018)
Article
Biochemistry & Molecular Biology
Atheer Zgair, Yousaf Dawood, Suhaib M. Ibrahem, Jong Bong Lee, Wanshan Feng, Peter M. Fischer, Pavel Gershkovich
Summary: It was found that the natural fruit extract of strawberry can inhibit the degradation of oral testosterone undecanoate (TU), potentially increasing the bioavailability of testosterone. Co-administration with strawberry extract may enhance the intestinal stability of TU, leading to increased contribution of lymphatic delivery of TU to systemic exposure of testosterone in vivo.
Article
Chemistry, Medicinal
Hao Shao, David W. Foley, Shiliang Huang, Abdullahi Y. Abbas, Frankie Lam, Pavel Gershkovich, Tracey D. Bradshaw, Chris Pepper, Peter M. Fischer, Shudong Wang
Summary: CDK9 is a crucial cyclin-dependent kinase involved in cell cycle and transcription regulation. The optimization of pyrimidine compounds as CDK9 inhibitors, particularly compound 30m, has shown significant selectivity and broad anti-proliferative activities. This research provides promising insights into potential treatments for various diseases involving CDK9 dysregulation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ziad Omran, Chris P. Guise, Linwei Chen, Cyril Rauch, Ashraf N. Abdalla, Omeima Abdullah, Ikhlas A. Sindi, Peter M. Fischer, Jeff B. Smaill, Adam V. Patterson, Yuxiu Liu, Qingmin Wang
Summary: Phenanthroindolizidines are natural alkaloids with pronounced cytotoxicity against human cancerous cell lines, but are associated with neurotoxicity and loss of in vivo activity. By developing them as hypoxia-targeted prodrugs, their cytotoxicity can be increased while minimizing other side effects.
Article
Pharmacology & Pharmacy
Wanshan Feng, Chaolong Qin, Elena Cipolla, Jong Bong Lee, Atheer Zgair, Yenju Chu, Catherine A. Ortori, Michael J. Stocks, Cris S. Constantinescu, David A. Barrett, Peter M. Fischer, Pavel Gershkovich
Summary: Oral sesame oil-based formulation helps deliver CBD to the lymphatic system and blood circulation, but also leads to variability in absorption. Adding MCT to the formulation increases CBD distribution into the micellar phase, while surfactants do not further enhance this distribution. MCT improves emulsification and micellar solubilization of CBD, reducing variability in concentrations in vivo.
Article
Pharmacology & Pharmacy
Adelaide Jewell, Alice Brookes, Wanshan Feng, Marianne Ashford, Paul Gellert, James Butler, Peter M. Fischer, David J. Scurr, Michael J. Stocks, Pavel Gershkovich
Summary: This study assessed the distribution of highly lipophilic drug cannabidiol (CBD) in specific mesenteric lymph nodes (MLN) and retroperitoneal lymph nodes (RPLN) following oral administration with lipids. The results showed that CBD concentrations were significantly higher in the region second from the apex of the MLN chain at 2 hours post dosing. From 3 hours post dosing, concentrations in all MLN were similar. CBD was also found at substantial levels in RPLN.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Chemistry, Medicinal
Jillian G. Baker, Christophe Fromont, Marjorie Bruder, Kevin S. J. Thompson, Barrie Kellam, Stephen J. Hill, Sheila M. Gardiner, Peter M. Fischer
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2020)
