Article
Biochemistry & Molecular Biology
Ilya S. Zhukov, Larisa G. Kubarskaya, Inessa Karpova, Anastasia N. Vaganova, Marina N. Karpenko, Raul R. Gainetdinov
Summary: Trace amine-associated receptor 5 (TAAR5) plays a crucial role in perceiving odors, regulating emotions, and potentially treating neuropsychiatric disorders. Research suggests that TAAR5 deficiency may lead to minor negative effects on hematological parameters, while having minimal impact on other blood-related factors. Further study is needed to fully understand the implications of TAAR5 gene knockout in erythropoiesis and eryptosis processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Carlotta Bon, Ting-Rong Chern, Elena Cichero, Terrence E. O'Brien, Stefano Gustincich, Raul R. Gainetdinov, Stefano Espinoza
Summary: Trace amine-associated receptor 5 (TAAR5) is expressed in the olfactory epithelium and limbic brain regions, and is involved in the regulation of emotional behavior and adult neurogenesis. Two identified mTAAR5 antagonists inhibit TMA-induced cAMP production and downstream signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lingna Guo, Wenxuan Dai, Zhengrong Xu, Qiaoyi Liang, Eliot T. Miller, Shengju Li, Xia Gao, Maude W. Baldwin, Renjie Chai, Qian Li
Summary: The family of trace amine-associated receptors (TAARs) is distantly related to G protein-coupled biogenic aminergic receptors. They are found in the brain and olfactory epithelium, and their functional relationships in different subfamilies and species are still uncertain. Through phylogenetic analysis, this study reveals the evolutionary patterns and ligand recognition profiles of TAARs and shows functional convergence and segregation in different species.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Review
Behavioral Sciences
Seetal Dodd, Andre F. Carvalho, Basant K. Puri, Michael Maes, Chiara C. Bortolasci, Gerwyn Morris, Michael Berk
Summary: TAARs are a group of receptors with multiple subfamilies that play important roles in homeostasis, olfaction, and monoamine systems. They are potential therapeutic targets for various mental disorders and cancers. Modulators of TAAR1 show efficacy in animal models, but further research is needed to establish their applicability.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Mikhail Krasavin, Alexey Lukin, Ilya Sukhanov, Andrey S. Gerasimov, Savelii Kuvarzin, Evgeniya V. Efimova, Mariia Dorofeikova, Anna Nichugovskaya, Andrey Matveev, Kirill Onokhin, Konstantin Zakharov, Maxim Gureev, Raul R. Gainetdinov
Summary: This study screened an in-house library of compounds for agonistic activity towards TAAR1, resulting in the discovery of a potent TAAR1 agonist. Further in vivo tests demonstrated its efficacy in schizophrenia-related experiments. More preclinical studies are needed to evaluate its potential as a pharmacotherapy option for schizophrenia and other psychiatric disorders.
Article
Biochemistry & Molecular Biology
Ilya S. S. Zhukov, Anastasia N. N. Vaganova, Ramilya Z. Z. Murtazina, Lyubov S. S. Alferova, Elena I. I. Ermolenko, Raul R. R. Gainetdinov
Summary: Trace amine-associated receptors (TAAR1-TAAR9) play an important role in the central nervous system and TAAR9 deletion leads to alterations in the periphery. TAAR9 is identified in intestinal tissues and is co-expressed with genes involved in intestinal mucosa homeostasis and function. Furthermore, TAAR9 may play a role in regulating peripheral dopaminergic transmission. Fecal microbiome analysis shows significant differences in the microbial composition between TAAR9-KO and wild-type rats, with certain bacterial families almost completely absent in TAAR9-KO rats.
Article
Biochemistry & Molecular Biology
Ramilya Z. Murtazina, Ilya S. Zhukov, Olga M. Korenkova, Elena A. Popova, Savelii R. Kuvarzin, Evgeniya V. Efimova, Larisa G. Kubarskaya, Ekaterina G. Batotsyrenova, Ekaterina A. Zolotoverkhaya, Anastasia N. Vaganova, Sergey A. Apryatin, Natalia V. Alenina, Raul R. Gainetdinov
Summary: The study found no significant effects of TAAR9 on hematological and most biochemical parameters, but revealed a significant decrease in total and low-density lipoprotein cholesterol levels in the blood of TAAR9-KO rats. This suggests a potential new drug target for disorders related to cholesterol regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Evgeniya V. Efimova, Alena A. Kozlova, Valeria Razenkova, Nataliia V. Katolikova, Kristina A. Antonova, Tatyana D. Sotnikova, Natalia S. Merkulyeva, Aleksandr S. Veshchitskii, Daria S. Kalinina, Dmitry E. Korzhevskii, Pavel E. Musienko, Evgeny V. Kanov, Raul R. Gainetdinov
Summary: TAAR5 is not only involved in the regulation of emotional status, but also adult neurogenesis and dopamine transmission. TAAR5-KO mice showed an increased number of proliferating neurons in the major neurogenic areas, suggesting that future TAAR5 antagonists may provide new treatment opportunities for neurodegenerative disorders like Parkinson's disease.
Review
Biochemistry & Molecular Biology
Anastasia N. Vaganova, Taisiia S. Shemyakova, Karina V. Lenskaia, Roman N. Rodionov, Charlotte Steenblock, Raul R. Gainetdinov
Summary: Currently, the treatment of metabolic syndrome primarily focuses on pharmacological symptom relief and complex lifestyle changes. This study explores the role of trace amines and their receptor systems, particularly trace amine-associated receptor 1 (TAAR1), in the pathogenesis of metabolic syndrome and the regulation of insulin secretion in pancreatic islets. The findings suggest that TAAR1 agonists have a positive effect on the progression of metabolic syndrome and the development of related diseases. Additionally, the expression of TAARs and the deregulation of their functional associations were found to be different in patients with metabolic diseases compared to healthy donors, indicating their potential as therapeutic targets.
Article
Agriculture, Multidisciplinary
Yuna Lee, Akihiro Nakano, Yuki Nagasato, Takashi Ichinose, Toshiro Matsui
Summary: The tripeptides YPG and YPP, with AdipoR1 agonistic YP sequences, have the potential to act as alternative adiponectin-like molecules by preferentially binding to AdipoR1 and promoting glucose uptake.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Savelii R. Kuvarzin, Ilya Sukhanov, Kirill Onokhin, Konstantin Zakharov, Raul R. Gainetdinov
Summary: SEP-363856 (Ulotaront) is a novel antipsychotic drug that acts on trace amine-associated receptor 1 and serotonin 5-HT1A receptors instead of dopamine D2 receptors. Clinical studies have shown that Ulotaront can effectively reduce both positive and negative symptoms of schizophrenia without causing typical side effects associated with other antipsychotic medications.
Article
Clinical Neurology
Icaro Raony, Ivan Domith, Mychael Lourenco, Roberto Paes-de-Carvalho, Pablo Pandolfo
Summary: The expression of TAAR1 is downregulated in ADHD rats, and its antagonist impairs cognitive performance, while the full agonist reduces motor hyperactivity and induces anxiolytic behavior. These findings suggest that TAAR1 may play an important role in the neurobiology of ADHD.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Ann M. Decker, Marcus F. Brackeen, Aida Mohammadkhani, Chad M. Kormos, David Hesk, Stephanie L. Borgland, Bruce E. Blough
Summary: The article reports the discovery of a hTAAR1 antagonist with potential for disease treatment, showing good pharmacological effects and mechanisms.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Cell Biology
Maria Qatato, Vaishnavi Venugopalan, Alaa Al-Hashimi, Maren Rehders, Aaron D. Valentine, Zeynep Hein, Uillred Dallto, Sebastian Springer, Klaudia Brix
Summary: The study revealed the localization of Taar1 in thyroid cells at the apical and ciliary extensions, where it may signal from. Chimeric mTaar1-EGFP forms high molecular mass forms, such as homodimers and tetramers, and only monomeric mTaar1-EGFP is biotinylated on the cell surface in polarized human thyrocytes. The trafficking of mTaar1 to cilia depends on their integrity.
Article
Chemistry, Organic
Jiyun Sun, Jiahui Chen, Katsushi Kumata, Zhiwei Xiao, Jian Rong, Ahmed Haider, Tuo Shao, Lu Wang, Hao Xu, Ming-Rong Zhang, Steven H. Liang
Summary: The study introduced a C-11-labeled TAAR1 high-affinity antagonist for PET imaging, but it lacked in vivo specificity due to fast metabolic degradation. Further research is needed to identify a suitable TAAR1 PET tracer for the development of TAAR1-directed therapeutic agents.
TETRAHEDRON LETTERS
(2021)
Review
Cell Biology
Tiemin Liu, Yong Xu, Chun-Xia Yi, Qingchun Tong, Dongsheng Cai
Summary: This review highlights the link between brain dysfunction and genetic mutations, sex, brain inflammation, microbiota, and stress as causes of whole-body pathophysiology. Studies suggest that dysfunction in the brain's perception and processing of internal and external cues can have profound effects on metabolism and other physiological functions.
Article
Endocrinology & Metabolism
Adina Sophie Graffunder, Sarah Paisdzior, Robert Opitz, Kostja Renko, Peter Kuehnen, Heike Biebermann
Summary: MCT8 is a crucial thyroid hormone transporter involved in fetal development. By introducing a TC-tag in the MCT8 protein, it is possible to monitor its expression in real time in cell culture models, potentially leading to the development of stable hiPSC MCT8 reporter lines for future studies.
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
(2022)
Review
Endocrinology & Metabolism
Peter Kuhnen, Heike Biebermann, Susanna Wiegand
Summary: This review discusses pharmacological therapeutic options for obese children and adolescents and compares them with conservative treatment approaches. Understanding underlying molecular mechanisms can help identify effective antiobesity drugs and modify current treatment strategies to assist obese children and adolescents in losing weight.
HORMONE RESEARCH IN PAEDIATRICS
(2022)
Article
Nanoscience & Nanotechnology
Shanshan Guo, Fernando Cazarez-Marquez, Han Jiao, Ewout Foppen, Nikita L. Korpel, Anita E. Grootemaat, Nalan Liv, Yuanqing Gao, Nicole van der Wel, Bing Zhou, Guangjun Nie, Chun-Xia Yi
Summary: This study introduces a method using lipid and polymer hybridized nanoparticles for local delivery of small interfering RNA (siRNA) to silence specific microglial genes in the hypothalamus. The researchers demonstrated the effectiveness of this method both in vitro and in vivo, showing significant reductions in gene expression and microglial activation.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Paul de Goede, Rob C. Wust, Bauke Schomakers, Simone Denis, Frederic M. Vaz, Mia L. Pras-Raves, Michel Weeghel, Chun-Xia Yi, Andries Kalsbeek, Riekelt H. Houtkooper
Summary: Shift-work disrupts circadian timing of glucose homeostasis, impairs muscle mitochondrial metabolism, and causes metabolic inflexibility, increasing the risk of developing T2DM.
Article
Toxicology
Louise Ramhoj, Terje Svingen, Caroline Fraedrich, Eddy Rijntjes, Eva K. Wirth, Katrine Pedersen, Josef Koehrle, Marta Axelstad
Summary: Disruption of thyroid hormone system during development can cause irreversible damage to brain development. This study found that TPO-inhibitors like methimazole and amitrole can induce similar effects on brain development in rats, driven by T4 deficiency.
TOXICOLOGY LETTERS
(2022)
Editorial Material
Endocrinology & Metabolism
Josef Koehrle, Martina Rauner, Susan A. Lanham-New
ENDOCRINE CONNECTIONS
(2022)
Article
Biochemistry & Molecular Biology
Eirini Vagena, Jasmina Crneta, Pauline Engstrom, Li He, Ernie Yulyaningsih, Nikita L. Korpel, Rachel T. Cheang, Tomas P. Bachor, Alyssa Huang, Guillermina Michel, Kush Attal, David Berrios, Martin Valdearcos, Suneil K. Koliwad, David P. Olson, Chun-Xia Yi, Allison W. Xu
Summary: Variants in the ASB4 gene are associated with human obesity. ASB4 acts in the brain to improve glucose homeostasis and induce satiety.
Article
Biochemistry & Molecular Biology
Nour Diab, Sameer Desale, Mark Danielsen, Josef Koehrle, Nawar Shara, Jacqueline Jonklaas
Summary: This study examined the relationship between thyroid hormone metabolites, specifically 3,5-diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM). The results suggest that there is a positive correlation between 3,5-T2 and T4/FT4 during liothyronine therapy, indicating that 3,5-T2 may be produced from endogenous T4. Additionally, the study found a negative correlation between T3 levels and 3-T1AM, but a positive correlation between 3,5-T2 levels and 3-T1AM, supporting the hypothesis that 3-T1AM is produced via 3,5-T2 with negative regulation by T3.
Review
Biochemistry & Molecular Biology
Joshua Seifert, Yingfu Chen, Wenzel Schoening, Knut Mai, Frank Tacke, Joachim Spranger, Josef Koehrle, Eva Katrin Wirth
Summary: This comprehensive review summarizes the effects of nutritional intervention and thyroid hormones on liver metabolism, specifically focusing on glucose, lipid, and cholesterol metabolism. Understanding these complex regulatory networks can potentially aid in the development of treatment options for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis involving thyroid hormone mimetics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Josef Koehrle
Summary: The availability and metabolism of iodine, selenium, and iron are essential for the function of the thyroid hormone system. Imbalances in these elements can lead to common diseases related to disrupted thyroid hormone status. Iodide is accumulated and incorporated into thyroglobulin, while selenium proteins defend against oxidative stress. The pituitary hormone thyrotropin regulates thyroid hormone synthesis and secretion. Deficiencies in these nutrients can be prevented with education and political measures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Tze Ping Loh, Joel Ehrenkranz, David Halsall, Carole Ann Spencer, Katleen Van Uytfanghe, Josef Koehrle
Article
Multidisciplinary Sciences
Patricia Gerhardt, Sabine Begall, Caroline Fraedrich, Kostja Renko, Thomas B. Hildebrandt, Susanne Holtze, Alexandra Heinrich, Arne Sahm, Xheni Meci, Josef Koehrle, Eddy Rijntjes, Yoshiyuki Henning
Summary: African mole-rats have adapted to the challenges of living underground by evolving low basal metabolism and body temperature. Their unique thyroid hormone phenotype and adaptations to the subterranean habitat were studied by comparing two mole-rat species with the house mouse as a laboratory model. Surprisingly, despite species-specific differences, both mole-rat species showed similar serum thyroid hormone concentrations. This study provides important insights into understanding adaptations to the subterranean habitat.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Irina Milanova, Nikita L. Korpel, Felipe Correa-da-Silva, Eline Berends, Samar Osman, Susanne E. la Fleur, Eric Fliers, Andries Kalsbeek, Chun-Xia Yi
Summary: The study found that microglial insulin signaling plays a role in the control of systemic energy balance and this function is sex-dependent. Lack of microglial InsR can lead to increased plasma insulin levels and insulin resistance in female obese mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Toxicology
Kostja Renko, Helena Kerp, Janina Pape, Eddy Rijntjes, Tanja Burgdorf, Dagmar Fuehrer, Josef Koehrle
Summary: Animal studies often describe the state of the thyroid hormone axis based on circulating hormone concentrations, ignoring local mechanisms. This study measured deiodinase and iodotyrosine deiodinase activity using a new method and identified organ-specific regulation patterns in different age groups.
FRONTIERS IN TOXICOLOGY
(2022)