Review
Pharmacology & Pharmacy
Martin Kaczocha, Samir Haj-Dahmane
Summary: The endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide are well-studied lipid messengers in the brain, influencing physiological and behavioural processes by activating cannabinoid receptors. Synthesized by postsynaptic neurons, endocannabinoids serve as retrograde messengers that suppress neurotransmitter release at central synapses. While the mechanisms governing endocannabinoid transport remain poorly defined, recent studies have started to unravel the complexities of intracellular and intercellular endocannabinoid transport mechanisms.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Mohammad Fauzan, Saida Oubraim, Mei Yu, Sherrye T. Glaser, Martin Kaczocha, Samir Haj-Dahmane
Summary: Endocannabinoids are endogenous lipid neurotransmitters that regulate various physiological functions. Fatty acid-binding protein 5 (FABP5) is a key regulator of intracellular endocannabinoid transport and inactivation. This study found that FABP5 controls endocannabinoid signaling in different brain regions, including the striatum and prefrontal cortex.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Chaoling Chen, Weili Wang, Justin L. Poklis, Aron H. Lichtman, Joseph K. Ritter, Gaizun Hu, Dengpiao Xie, Ningjun Li
Summary: The study suggests that FAAH activation and the consequent reduction of AEA contribute to renal fibrogenesis, while FAAH inhibition protects against fibrogenesis in renal cells independently of CB receptors via the AEA-COX-2 pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Clinical Neurology
Hajar Mikaeili, Abdella M. Habib, Charlix Wai-Lok Yeung, Sonia Santana-Varela, Ana P. Luiz, Kseniia Panteleeva, Sana Zuberi, Alkyoni Athanasiou-Fragkouli, Henry Houlden, John N. Wood, Andrei L. Okorokov, James J. Cox
Summary: Mikaeili et al. have identified the molecular basis of pain insensitivity associated with FAAH-OUT. This discovery provides insights into the regulation of pain and offers potential for new gene therapy approaches. Chronic pain affects millions of people worldwide and requires urgent treatment options.
Article
Genetics & Heredity
Lisa Bornscheuer, Andreas Lundin, Yvonne Forsell, Catharina Lavebratt, Philippe A. Melas
Summary: This study explores the relationship between fatty acid amide hydrolase (FAAH) and subjective well-being, and found a functional polymorphism in the FAAH gene to be associated with decreased well-being and increased alcohol dependence. The findings suggest that chronically elevated levels of anandamide may disrupt the well-being system, leading to increased alcohol intake.
Review
Biochemistry & Molecular Biology
Julia Nowowiejska, Anna Baran, Iwona Flisiak
Summary: This study discusses the role of fatty-acid-binding proteins (FABPs) in psoriasis and their potential as markers. Due to the different expressions and functions of FABPs in various tissues, they may be associated with psoriasis and its comorbidities.
Article
Nutrition & Dietetics
Guojun Wu, Hiba R. Tawfeeq, Atreju I. Lackey, Yinxiu Zhou, Zoe Sifnakis, Sophia M. Zacharisen, Heli Xu, Justine M. Doran, Harini Sampath, Liping Zhao, Yan Y. Lam, Judith Storch
Summary: This study investigated the effects of LFABP and IFABP deficiency on the gut microbiota in mice, and found that these changes were associated with phenotypic changes induced by a high-fat diet.
Article
Cell Biology
Liang-Ti Huang, Hsiu-Chu Chou, Chung-Ming Chen
Summary: Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants characterized by interrupted alveologenesis and alveolar simplification due to oxygen therapy. The study found that the FABP4 inhibitor BMS309403 can regulate pulmonary fibrotic processes in newborn rats exposed to hyperoxia, reducing lung fibrosis and expression of TGF-beta 1. The inhibition of FABP4 showed potential clinical and therapeutic applications in attenuating hyperoxia-induced lung impairments.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Neurosciences
Karla Chavira-Ramos, Mario Orozco-Morales, Cimen Karasu, Alexey A. Tinkov, Michael Aschner, Abel Santamaria, Ana Laura Colin-Gonzalez
Summary: Endocannabinoid-based therapies show potential as a tool for treating neurodegenerative disorders, with experimental studies demonstrating the neuroprotective properties of the FAAH inhibitor URB597 in preventing early toxic effects induced by QUIN in rat cortical tissue. The protective effects of URB597 were found to be mediated by the activation of CB1 receptors and were similar to those observed with AEA, suggesting a potential link between FAAH inhibition and the protective effects of endocannabinoids.
NEUROTOXICITY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Agnes Angyal, Zsofia Penzes, Shahrzad Alimohammadi, Dorottya Horvath, Lili Takacs, Gyorgy Vereb, Barbara Zsebik, Tamas Biro, Kinga Fanni Toth, Erika Lisztes, Balazs Istvan Toth, Attila Olah, Attila Gabor Szollosi
Summary: The study found that human corneal epithelial cells express members of the endocannabinoid system, playing a role in inflammatory responses. Despite previous reports on the anti-inflammatory potential of endocannabinoids, their effects on the immune phenotype of human corneal epithelium may be more complex and context dependent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Ahmad Mobed, Fereshteh Kohansal, Ali Ahmadalipour, Mohammad Hasanzadeh, Flor Zargari
Summary: This study developed an immunosensor for detecting endocannabinoids 2-AG in human plasma samples, which can accurately determine the concentration of 2-AG in different ranges through monitoring the antigen in an immunoreaction process.
ANALYTICAL METHODS
(2021)
Article
Neurosciences
Douglas J. Hermes, Barkha J. Yadav-Samudrala, Changqing Xu, Jacqueline E. Paniccia, Rick B. Meeker, Michael L. Armstrong, Nichole Reisdorph, Benjamin F. Cravatt, Ken Mackie, Aron H. Lichtman, Bogna M. Ignatowska-Jankowska, Donald T. Lysle, Sylvia Fitting
Summary: This study investigated the role of FAAH inhibition in microglial neurotoxicity induced by HIV-1 Tat protein. The results demonstrated that the FAAH inhibitor PF3845 effectively attenuated the neurotoxic effects, leading to neuroprotection of neurons from damage.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Pharmacology & Pharmacy
Anitha Police, Vijay Kumar Shankar, Pankaj Pandey, Srinath Rangappa, Robert J. Doerksen, S. Narasimha Murthy
Summary: Peripheral neuropathy (PN) is a condition characterized by peripheral nerve damage leading to severe pain. The current treatments for PN have either psychotropic side effects or are not effective enough. This study aims to find a safe inhibitor of the fatty acid amide hydrolase enzyme (FAAH) and develop a topical gel formulation to deliver anandamide, an endocannabinoid that relieves PN pain. The results showed that silymarin constituents, particularly silybin, demonstrated significant FAAH inhibition potential and increased the half-life of anandamide. The developed gel formulation increased the permeation of anandamide and silybin, resulting in a significant increase in pain threshold in rat models of PN.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Neuroimaging
Kevin M. Crombie, Anthony A. Privratsky, Chloe M. Schomaker, Mickela Heilicher, Marisa C. Ross, Anneliis Sartin-Tarm, Kyrie Sellnow, Elisabeth B. Binder, G. Andrew James, Josh M. Cisler
Summary: This study found that genetic variation in the FAAH gene influences the physiological, cognitive, and neural fear learning characteristics in women with PTSD. Different genotypes showed divergent physiological and neural responses, suggesting that targeting FAAH may be a promising therapeutic approach for PTSD.
NEUROIMAGE-CLINICAL
(2022)
Review
Pharmacology & Pharmacy
William George Warren, Myles Osborn, Andy Yates, Karen Wright, Saoirse E. O'Sullivan
Summary: Fatty acid binding protein 5 (FABP5) is an intracellular chaperone that regulates lipid metabolism and cell growth. Increased expression of FABP5 is associated with poor prognosis in tumors, and inhibiting FABP5 reduces protumoral markers, making it a potential therapeutic target. The strongest evidence base currently exists for liver, prostate, breast, brain cancers, and squamous cell carcinoma (SCC).
DRUG DISCOVERY TODAY
(2023)
Article
Biochemistry & Molecular Biology
Lin Bai, Huilin Li
Summary: Membrane proteins' transmembrane alpha-helices come in highly hydrophobic and less hydrophobic forms, with insertion into the membrane requiring different insertase enzymes. Recent cryo-electron microscopy studies have shown structural conservation of the endoplasmic reticulum membrane complex (EMC) from yeast to humans, a common substrate-binding pocket, and evolutionary similarities to prokaryotic insertases. These findings offer a foundation for future mechanistic research.
Article
Neurosciences
Taygun C. Uzuneser, Hanna J. Szkudlarek, Matthew J. Jones, Mina G. Nashed, Timothy Clement, Hehe Wang, Iwao Ojima, Walter J. Rushlow, Steven R. Laviolette
Summary: This study identifies FABP-5 inhibition as a potential target for treating anxiety disorders. It also uncovers a novel CB2R-dependent FABP-5 signaling pathway in the prefrontal cortex (PFC) that strongly modulates anxiety-related behaviors and neuronal transmission patterns.
Correction
Oncology
Xiaowei Zheng, Changwei Wang, Yuanming Xing, Siying Chen, Ti Meng, Haisheng You, Iwao Ojima, Yalin Dong
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Feng Wang, Xiang Feng, Qing He, Hua Li, Huilin Li
Summary: In this study, cryo-EM analysis revealed that the Saccharomyces cerevisiae Yta7 protein assembles into a three-tier hexamer structure, consisting of a top bromodomain (BRD) tier, a middle AAA1 tier, and a bottom AAA2 tier. The BRD of Yta7 stabilizes a four-stranded beta-helix structure called BRD-interacting motif (BIM) in the N-terminal region. Both the BRD and BIM contribute to nucleosome recognition and Yta7 binds to both acetylated and nonacetylated H3 peptides with higher affinity for the unmodified peptide. Overall, this study provides insights into the nucleosome disassembly process by Yta7.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hua Li, Digantkumar Chapla, Robert A. Amos, Annapoorani Ramiah, Kelley W. Moremen, Huilin Li
Summary: In this study, the structure of the human EXT1-EXT2 heterocomplex was determined in the presence of donor and acceptor substrates. The results showed that only two out of the four glycosyltransferase domains were major contributors to co-polymer syntheses, namely the EXT1 GT-B fold beta 1,4GlcA transferase domain and the EXT2 GT-A fold alpha 1,4GlcNAc transferase domain.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Genetics & Heredity
Petr Daniel, Kamila Balusikova, Radka Vaclavikova, Karolina Seborova, Sarka Ransdorfova, Marie Valerianova, Longfei Wei, Michael Jelinek, Tereza Tlapakova, Thomas Fleischer, Vessela N. N. Kristensen, Pavel Soucek, Iwao Ojima, Jan Kovar
Summary: Limited studies have focused on regulating TRIP6 expression in cancer. This study aimed to investigate the regulation of TRIP6 expression in MCF-7 breast cancer cells and taxane-resistant sublines. The findings suggest that the transcription of TRIP6 is primarily regulated by the cyclic AMP response element (CRE) in hypomethylated proximal promoters, and TRIP6 overexpression is associated with co-amplification with the neighboring ABCB1 gene in taxane-resistant cells. Moreover, high levels of TRIP6 mRNA were found in progesterone receptor-positive breast cancer and samples from premenopausal women.
Article
Biochemistry & Molecular Biology
Lin Bai, Huilin Li
Summary: Certain transmembrane α-helices of multi-pass membrane proteins have partially hydrophilic regions that form substrate transport paths or catalytic pockets. Sec61 alone is insufficient for inserting these less hydrophobic segments into the membrane and requires dedicated membrane chaperones. Recent structural studies on these chaperones provide insights into the poorly understood process of multi-pass membrane protein biogenesis, including their architecture, multi-subunit assembly, substrate transmembrane helix-binding pockets, and cooperative mechanisms with ribosomes and Sec61 translocons.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
Kalani Jayanetti, Kathryn Takemura, Hersh Bendale, Ashna Garg, Iwao Ojima
Summary: This article discusses the strategic incorporation of fluorine and organofluorine moieties into new-generation taxoid anticancer agents. The study shows that these fluorotaxoids exhibit high potency against drug-resistant cancer cell lines, making them promising candidates for chemotherapy.
JOURNAL OF FLUORINE CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Feng Wang, Qing He, Wenhu Zhan, Ziqi Yu, Efrat Finkin-Groner, Xiaojing Ma, Gang Lin, Huilin Li
Summary: The human UBR5 is a HECT-type E3 ubiquitin ligase essential for embryonic development in mammals. Dysregulated UBR5 functions as an oncoprotein to promote cancer growth and metastasis. This study reveals the assembly of UBR5 into a dimer and a tetramer, providing insights into its structure and potential anticancer drug development.
Article
Microbiology
Nivea Pereira de Sa, Kalani Jayanetti, Dominick Rendina, Timothy Clement, Veronica Soares Brauer, Caroline Mota Fernandes, Iwao Ojima, Michael V. Airola, Maurizio Del Poeta
Summary: Invasive fungal infections are a leading cause of death in immunocompromised patients. We studied the fungus-specific enzyme SglA as a therapeutic target and identified selective inhibitors that delay filamentation in the pathogenic fungus and increase survival in a murine model of pulmonary aspergillosis.
Article
Biochemistry & Molecular Biology
Chuanzhou Zhu, Livia Schutz, Kalani Jayanetti, Kathryn Takemura, Faniya Doswell, Liqun Wang, Iwao Ojima, Martin Kaczocha
Summary: This study describes the synthesis and biological evaluation of truxillic acid monoamides (TAMADs) as potent, selective, and efficacious FABP5 inhibitors. The results demonstrate that TAMADs exhibit exceptional selectivity against FABP3 and possess high affinities for FABP5. Antinociceptive activity analysis reveals comparable efficacy and temporal activity profiles of TAMADs and their corresponding TAMEs in vivo.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Xiang Feng, Michelle M. Spiering, Ruda de Luna Almeida Santos, Stephen J. Benkovic, Huilin Li
Summary: The authors demonstrate the assembly process of the T4 primosome, consisting of gp41 helicase and gp61 primase, using cryo-EM structures. They show that gp41 undergoes a conformational change upon ssDNA binding, leading to ring closure and helicase activation. The activated helicase recruits the gp61 primase through a bipartite binding mode, resulting in the assembly of the primosome on the helicase hexamer.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
E. Sethe Burgie, Hua Li, Zachary T. K. Gannam, Katrice E. E. McLoughlin, Richard D. D. Vierstra, Huilin Li
Summary: The three-dimensional model of phytochrome A reveals a new signaling mechanism and structural diversification among isoforms that extends light and temperature perception. Phytochrome A is better suited for sensing dim light, while Phytochrome B is more adapted for detecting full sun and temperature.
Article
Plant Sciences
E. Sethe Burgie, Hua Li, Zachary T. K. Gannam, Katrice E. McLoughlin, Richard D. Vierstra, Huilin Li
Summary: The three-dimensional model of phytochrome A reveals its role in a new signaling mechanism and how structural diversification among isoforms enhances light and temperature perception in plants.
Meeting Abstract
Oncology
Radka Vaclavikova, Karolina Seborova, Alzbeta Spalenkova, Marie Ehrlichova, Iwao Ojima, Petr Daniel, Jan Kovar, Pavel Soucek
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2022)