Review
Pharmacology & Pharmacy
Fang-Yuan Wang, Ping Wang, Dong-Fang Zhao, Frank J. Gonzalez, Yu-Fan Fan, Yang-Liu Xia, Guang-Bo Ge, Ling Yang
Summary: This review summarizes recent advances in analytical methodologies for sensing COMT activity and their applications, while highlighting challenges and future perspectives in the field. The practical assays for measuring COMT activities in complex biological samples are crucial for investigating the relevance of COMT to human diseases and promoting the discovery of COMT inhibitors via high-throughput screening.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2021)
Article
Biochemistry & Molecular Biology
Andries D. de Beer, Lesetja J. Legoabe, Anel Petzer, Jacobus P. Petzer
Summary: Enzymes COMT and MAO are key drug targets for treating Parkinson's disease. This study identified compounds that can inhibit both COMT and MAO-B, with 4-chromanone derivative (7) and 1-tetralone derivative (4d) showing the most promising results.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Fang-Yuan Wang, Gui-Lin Wei, Yu-Fan Fan, Dong-Fang Zhao, Ping Wang, Li-Wei Zou, Ling Yang
Summary: In this study, oleanic acid, betulinic acid, and celastrol were identified as potent inhibitors of COMT with the ability to specifically recognize and bind with the enzyme, while reducing the risk of liver toxicity. These findings could lead to the development of new lead compounds and derivatives for further testing.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Andrea Polli, Jolien Hendrix, Kelly Ickmans, Jelena Bakusic, Manosij Ghosh, Dora Monteyne, Brigitte Velkeniers, Bram Bekaert, Jo Nijs, Lode Godderis
Summary: The study found associations between COMT haplotypes and DNA methylation, cytokine expression, and symptoms in patients with CFS/FM, but not specific to one condition. Significant differences were observed in increased DNA methylation in the MB-COMT promoter and decreased IFN-gamma expression in patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Chuan-Ming Li, Le Chen, Guanjie Chen, Jianhua Zhang, Howard J. Hoffman
Summary: This study found a significant association between the COMT gene and hearing loss, with the A allele of rs6480 being linked to increased hearing loss. Among young adults in the United States, a missense variant of the COMT gene, rs4680, was significantly associated with hearing loss, shedding light on the genetic mechanisms of hearing loss.
Article
Behavioral Sciences
Courtney C. Louis, Mark D'Esposito, Jason S. Moser
Summary: This study found that worry is associated with reduced working memory, and dopamine in the prefrontal cortex heavily influences the stability of mental representations during working memory tasks. By using the COMT gene as a proxy for dopamine levels, the research demonstrated that basal dopamine plays an important role in how increases in worry negatively impact working memory performance over time.
COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
A. Katherine Hatstat, Grace M. Kennedy, Trevor R. Squires, Gisela Xhafkollari, C. Skyler Cochrane, Mauricio Cafiero, Larryn W. Peterson
Summary: L-DOPA, a dopamine precursor, is commonly used in Parkinson's disease treatment. Inhibiting COMT can prolong the effects of L-DOPA and dopamine, increasing the efficiency of the treatment. Nitrile derivatives with a nitro substituent show the most promise as COMT inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Johannie de Beer, Jacobus P. Petzer, Anna C. U. Lourens, Anel Petzer
Summary: The study focuses on developing non-nitrocatechol COMT inhibitors for the treatment of Parkinson's disease, aiming to prevent the metabolism of levodopa by COMT to enhance its effectiveness in the brain. By synthesizing a series of 3-hydroxypyridin-4-one compounds, it is demonstrated that they are potential inhibitors of COMT.
MOLECULAR DIVERSITY
(2021)
Article
Biochemistry & Molecular Biology
K. Poonkuzhali, R. Seenivasagan, J. Prabhakaran, A. Karthika
Summary: Chemically engineered PLGA nanospheres inhibiting Catechol-O-methyltransferase (COMT) are a promising technology for treating neurodegenerative disorders. PLGA-MATPM nanospheres, synthesized using PLGA and MATPM, effectively inhibit COMT in a dose-dependent manner. The interaction between COMT and PLGA nanospheres is explained through spectroscopic and molecular dynamics analysis. PLGA-MATPM nanospheres show neurodegenerative recovery by suppressing the growth of neuroblastoma cells and effectively cross the blood-brain barrier.
BIOORGANIC CHEMISTRY
(2023)
Review
Behavioral Sciences
Annabel Vetterlein, Merlin Monzel, Martin Reuter
Summary: The COMT gene has been considered as the pain sensitivity gene for almost two decades, but there is inconsistent evidence in the literature. Our meta-analyses of 31 samples and 4631 participants showed small effects of rs4680 on pain thresholds in fibromyalgia, headache, and chronic pain conditions. The effects of rs4680 were found in pain patients when affected body sites were assessed. No effects were found for other investigated SNPs. These results support the theory that rs4680 may only impact behavioral measures of pain under certain conditions.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Review
Endocrinology & Metabolism
Rosa Isela Ortiz-Huidobro, Myrian Velasco, Carlos Larque, Rene Escalona, Marcia Hiriart
Summary: The rise in obesity, particularly among women, is linked to insulin resistance in adipose tissue, a critical factor in metabolic diseases. Understanding the sexual dimorphism in molecular mechanisms of insulin actions is essential for developing targeted therapeutic strategies and public health policies to address obesity and diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Gastroenterology & Hepatology
Sarra Smati, Arnaud Polizzi, Anne Fougerat, Sandrine Ellero-Simatos, Yuna Blum, Yannick Lippi, Marion Regnier, Alexia Laroyenne, Marine Huillet, Muhammad Arif, Cheng Zhang, Frederic Lasserre, Alain Marrot, Talal Al Saati, JingHong Wan, Caroline Sommer, Claire Naylies, Aurelie Batut, Celine Lukowicz, Tiffany Fougeray, Blandine Tramunt, Patricia Dubot, Lorraine Smith, Justine Bertrand-Michel, Nathalie Hennuyer, Jean-Philippe Pradere, Bart Staels, Remy Burcelin, Francoise Lenfant, Jean-Francois Arnal, Thierry Levade, Laurence Gamet-Payrastre, Sandrine Lagarrigue, Nicolas Loiseau, Sophie Lotersztajn, Catherine Postic, Walter Wahli, Christophe Bureau, Maeva Guillaume, Adil Mardinoglu, Alexandra Montagner, Pierre Gourdy, Herve Guillou
Summary: The study found that different diets induced more severe NAFLD in male mice, characterized by lipid accumulation and inflammation/fibrosis. Sex-biased hepatic gene signatures showed different responses to various dietary challenges, with Peroxisome proliferator-activated receptor alpha (PPAR alpha) playing a key role in gender-specific and NAFLD pathophysiology.
Article
Pharmacology & Pharmacy
Yupin Su, Michael DePasquale, Gangling Liao, Ingrid Buchler, Gongliang Zhang, Spencer Byers, Gregory V. Carr, James Barrow, Huijun Wei
Summary: Selective inhibition of MBCOMT has shown promise in blocking dopamine metabolism, potentially improving cognitive deficits in disorders such as schizophrenia, ADHD, and traumatic brain injury.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biology
Nuria de Zavalia, Konrad Schoettner, Jory A. Goldsmith, Pavel Solis, Sarah Ferraro, Gabrielle Parent, Shimon Amir
Summary: The study reveals that the expression levels of Bmal1 and Per2 in the mouse striatum may have a gender-dependent impact on alcohol consumption propensity, with deletion of Bmal1 resulting in increased alcohol intake in males and decreased intake in females.
COMMUNICATIONS BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Isabella M. Salamone, Mattia Quattrocelli, David Y. Barefield, Patrick G. Page, Ibrahim Tahtah, Michele Hadhazy, Garima Tomar, Elizabeth M. McNally
Summary: Weekly glucocorticoid exposure produces different effects on skeletal muscle performance in male and female mice. Male muscles show enhanced response to weekly glucocorticoids, while female muscles exhibit significant upregulation of lipid metabolism genes.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Psychiatry
Maxime Taquet, John R. Geddes, Sierra Luciano, Paul J. Harrison
Summary: The study found that diagnostic incidence of eating disorders increased significantly during the COVID-19 pandemic, especially in females, teenagers, and those with anorexia nervosa. Additionally, a higher proportion of patients with eating disorders in 2020 had suicidal ideation and attempted suicide.
BRITISH JOURNAL OF PSYCHIATRY
(2022)
Editorial Material
Neurosciences
Nicola A. L. Hall, Elizabeth M. Tunbridge
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Clinical Neurology
Arne W. Mould, Noura Al-Juffali, Annette von Delft, Paul E. Brennan, Elizabeth M. Tunbridge
Summary: The study examines the role of kalirin in brain function and its therapeutic potential in schizophrenia, focusing on its regulation of synapse formation and stabilization. The need for further understanding of the diversity and function of its isoforms is highlighted, along with their changes across neurodevelopment and effects on brain function in vivo.
Article
Neurosciences
Judith Schweimer, Julia T. Brouard, Yan Li, Connie Sanchez, Trevor Sharp
Summary: The study found that vortioxetine inhibits 5-HT3R-INs and excites pyramidal neurons, thereby changing the balance between excitatory and inhibitory activity in the cortex.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
James S. W. Hong, Lauren Z. Atkinson, Noura Al-Juffali, Amine Awad, John R. Geddes, Elizabeth M. Tunbridge, Paul J. Harrison, Andrea Cipriani
Summary: Gabapentinoids like gabapentin and pregabalin target the alpha(2)delta subunits of voltage-gated calcium channels. There is moderate evidence for their efficacy in anxiety states, but minimal evidence in bipolar disorder and insomnia, therefore they should be used for these disorders only with strong justification. This recommendation applies despite the attractive pharmacological and genetic rationale for targeting voltage-gated calcium channels.
MOLECULAR PSYCHIATRY
(2022)
Article
Psychiatry
Livia J. De Picker, Marion Leboyer, John R. Geddes, Manuel Morrens, Paul J. Harrison, Maxime Taquet
Summary: This study suggests that patients with therapeutic levels of lithium have a lower risk of COVID-19 infection, regardless of underlying psychiatric diagnosis or vaccination status, based on electronic health records.
BRITISH JOURNAL OF PSYCHIATRY
(2022)
Article
Clinical Neurology
Marieke A. G. Martens, Nina Dalton, Jessica Scaife, Catherine J. Harmer, Paul J. Harrison, Elizabeth M. Tunbridge
Summary: Our study found that COMT has little or no effect on emotional processing or mood in healthy adult men, which contradicts some neuroimaging studies. However, novel COMT inhibitors for treating cognitive dysfunction are unlikely to have acute off target effects on emotional behaviors.
JOURNAL OF PSYCHOPHARMACOLOGY
(2022)
Article
Clinical Neurology
Paul J. Harrison, Maxime Taquet
Summary: Harrison and Taquet review the literature on neuropsychiatric diagnoses following COVID-19, focusing on depression, anxiety, psychosis, and cognitive impairment. They discuss key issues such as the level of risk increase and whether it varies based on gender or different SARS-CoV-2 strains. While some studies using electronic health records have reported higher rates of neuropsychiatric disorders after COVID-19, many questions remain.
Article
Biochemistry & Molecular Biology
Marios C. Panayi, Thomas Boerner, Thomas Jahans-Price, Anna Huber, Rolf Sprengel, Gary Gilmour, David J. Sanderson, Paul J. Harrison, Mark E. Walton, David M. Bannerman
Summary: Psychosis in disorders like schizophrenia is associated with aberrant salience and elevated striatal dopamine. The cause of this hyper-dopaminergic state is unknown. Deficits in glutamatergic function and synaptic plasticity may contribute to schizophrenia, including deficits associated with the GluA1 AMPAR subunit. This study shows that GluA1 dysfunction, resulting in impaired short-term habituation, is a key driver of enhanced striatal dopamine responses, which may contribute to aberrant salience and psychosis in psychiatric disorders.
MOLECULAR PSYCHIATRY
(2023)
Article
Neurosciences
Charlotte H. Harrison, Maxime Taquet, Paul J. Harrison, Peter J. Watkinson, Matthew J. Rowland
Summary: This study examines the antecedent characteristics of non-traumatic subarachnoid hemorrhage (SAH) patients, compares the risk of SAH between women and men, and investigates if this changes with age. The results show that men have a higher risk of SAH than women overall, particularly in younger adults. However, in the age group over 75 years, women have a higher risk of SAH compared to men.
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Paul J. Harrison, David M. Bannerman
Summary: The involvement of the glutamate system, particularly the NMDA receptor hypofunction, is considered to be part of the pathophysiology of schizophrenia. Recent data strongly implicate the gene GRIN2A, encoding the NR2A NMDA receptor subunit, in the development of schizophrenia. Both rare and common variants of this gene are associated with genetic risk for the disorder, and they are likely to result in reduced gene expression.
MOLECULAR PSYCHIATRY
(2023)
Review
Psychiatry
Caroline Zangani, Edoardo G. Ostinelli, Katharine A. Smith, James S. W. Hong, Orla Macdonald, Gurpreet Reen, Katherine Reid, Charles Vincent, Rebecca Syed Sheriff, Paul J. Harrison, Keith Hawton, Alexandra Pitman, Rob Bale, Seena Fazel, John R. Geddes, Andrea Cipriani
Summary: During the first year of the COVID-19 pandemic, mental health services quickly adapted and implemented or increased the use of telemental health services worldwide. However, limited access to digital devices, poor digital skills, and individual preferences and needs of patients may have resulted in differences in the implementation and accessibility of telemental health services during the pandemic. A blended approach that combines in-person and virtual modalities, taking into consideration the needs, preferences, and digital skills of patients, may better support the future development of mental health services.
JMIR MENTAL HEALTH
(2022)
Article
Clinical Neurology
Maxime Taquet, Paul J. Harrison
Summary: Post-COVID cognitive deficits, commonly known as 'brain fog,' can be prevented by inhibiting receptor-interacting protein kinase. Patients taking phenytoin at the time of COVID-19 infection have a lower risk of cognitive deficits compared to those taking valproate or levetiracetam. This finding supports further investigation of receptor-interacting protein kinase inhibitors in preventing post-COVID cognitive deficits.
BRAIN COMMUNICATIONS
(2022)