Article
Health Care Sciences & Services
Taichi Ochi, Natalya M. Vyalova, Innokentiy S. Losenkov, Diana Z. Paderina, Ivan Pozhidaev, Anton J. M. Loonen, German G. Simutkin, Nikolay A. Bokhan, Bob Wilffert, Svetlana A. Ivanova
Summary: This study found a possible association between genotype related to dopamine neurotransmission and antidepressant treatment response. DRD4 and MAOB genotypes were linked to improved HAMD 17 scores, but the preliminary nature of the results is noted due to the limited sample size. Further research into the role of habenular dopamine D4 receptors in antidepressant response is recommended.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Clinical Neurology
Gudrun Hefner, Jan Wolff, Sermin Toto, Pamela Reissner, Ansgar Klimke
Summary: Off-label drug prescribing in psychiatry is increasing and this study analyzed the prevalence and category of off-label use of psychotropic drugs. The results showed that 30.2% of patients received at least one off-label prescription during their hospital stay, and the off-label prevalence rates varied significantly among different diagnostic groups.
JOURNAL OF NEURAL TRANSMISSION
(2022)
Review
Medicine, General & Internal
Yue Hu, Fang Deng, Lupeng Zhang, Keyue Hu, Shiqi Liu, Suye Zhong, Jun Yang, Xiaomin Zeng, Xiaoning Peng
Summary: Depression is a common complication in patients with gliomas, and it can severely affect their psychological well-being and quality of life. Risk factors for depression in these patients include female sex, unmarried status, low education level, high tumor grade, and a history of mental illness. Antidepressant use can improve the prognosis of patients with gliomas.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Clinical Neurology
Marco Di Nicola, Maria Pepe, Silvia Montanari, Maria Chiara Spera, Isabella Panaccione, Alessio Simonetti, Gabriele Sani
Summary: This study evaluated the effects of vortioxetine after 1 and 3 months of treatment in patients with post-COVID-19 MDE. The results showed that vortioxetine improved physical symptoms, cognitive functioning, and reduced inflammatory markers. Therefore, vortioxetine might be a favorable therapeutic choice for post-COVID-19 patients with MDE.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Lara Coppi, Simona Ligorio, Nico Mitro, Donatella Caruso, Emma De Fabiani, Maurizio Crestani
Summary: Metabolism is crucial for providing energy and building blocks for cell functions, with mitochondria being the main site for energy production. PGC1 proteins play a key role in regulating cellular processes, particularly metabolic pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Letao Yang, Christopher Rathnam, Takuya Hidaka, Yannan Hou, Brandon Conklin, Ganesh N. Pandian, Hiroshi Sugiyama, Ki-Bum Lee
Summary: The study highlights the development of a nanoparticle-based synthetic mitochondrial transcription regulator (MitoScript) for controlling mitochondrial DNA transcription. MitoScript demonstrates great colloidal stability, biocompatibility, efficient cell uptake, and selective mitochondria targeting. It effectively downregulated the expression of the ND6 gene, which impacted the cell's redox status, resulting in increased ROS generation. This technology could contribute to understanding mitochondrial disorders and developing treatments for mitochondrial diseases.
Review
Cell Biology
Kunwar Somesh Vikramdeo, Sarabjeet Kour Sudan, Ajay P. Singh, Seema Singh, Santanu Dasgupta
Summary: Mitochondria play a crucial role in cellular energy production and signaling pathways, and alterations in respiratory complexes can lead to mitochondrial disorders and cancer development.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Clinical Neurology
Isak Joneborg, Yena Lee, Joshua D. Di Vincenzo, Felicia Ceban, Shakila Meshkat, Leanna M. W. Lui, Farhan Fancy, Joshua D. Rosenblat, Roger S. McIntyre
Summary: This article evaluates the efficacy of ketamine-assisted psychotherapy in the treatment of treatment-resistant depression and substance use disorders. Several clinical trials show that ketamine-assisted psychotherapy has a positive impact on primary outcome measures, although the data is mixed. The mechanisms of ketamine, such as NMDAR inhibition and increased synaptic neuroplasticity, are believed to contribute to its therapeutic effects.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Cell Biology
Josh Allen, Hector J. Caruncho, Lisa E. Kalynchuk
Summary: This study explores how chronic stress can induce depressive symptoms by affecting mitochondrial function, and how targeting mitochondrial defects may be a promising avenue for the development of more effective antidepressants.
Article
Gastroenterology & Hepatology
Sven H. Loosen, Pia Paffenholz, Tom Luedde, Karel Kostev, Christoph Roderburg
Summary: Studies in German outpatients have shown that patients with diverticular disease are more likely to develop depression and anxiety disorders, with a higher prescription rate for antidepressant drugs in this group compared to individuals without diverticular disease. These associations were observed across different age groups and both sexes, suggesting the importance of regular screening for symptoms of depression and anxiety disorders in patients with diverticular disease.
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Takayoshi Otsuka, Hideaki Matsui
Summary: Neurodegenerative disorders are characterized by progressive loss of neuronal structure or function, leading to memory loss and movement disorders. Small fish models, with their genetic and histological similarity to humans, in vivo imaging capabilities, and ease of genetic manipulation, have become ideal vertebrate models for studying human diseases. This review outlines the impact of mitochondrial dysfunction on neurodegenerative diseases, highlights the advantages of small fish models, and presents examples of previous studies on mitochondria-related neuronal disorders. The turquoise killifish, a unique model for aging research, is also discussed as a potential model for neurodegenerative diseases. Small fish models are expected to enhance our understanding of in vivo mitochondrial function and the pathogenesis of neurodegenerative diseases, and serve as important tools for developing therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Katja E. Menger, Alejandro Rodriguez-Luis, James Chapman, Thomas J. Nicholls
Summary: Mitochondrial genome (mtDNA) is a small DNA molecule present in human cells, playing a crucial role in mitochondrial gene expression and function. Topoisomerases are enzymes that modulate mtDNA topology, impacting mitochondrial function. Loss of topoisomerase activity can lead to defects in mitochondrial function.
Article
Pharmacology & Pharmacy
Marcin Siwek, Aleksandra Gorostowicz, Magdalena Bosak, Dominika Dudek
Summary: Epilepsy and depression often coexist, and there is a bidirectional relationship between the two disorders. However, current evidence on the effectiveness of antidepressant therapy in patients with epilepsy and comorbid depression is limited. Vortioxetine, a multimodal antidepressant, shows promise as a treatment option for depressed patients with cognitive dysfunctions, anhedonia, and anxiety.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mansoor Hussain, Xixia Chu, Burcin Duan Sahbaz, Samuel Gray, Komal Pekhale, Jae-Hyeon Park, Deborah L. Croteau, Vilhelm A. Bohr
Summary: Aging is associated with decreased DNA repair efficiency and increased inflammation, contributing to age-related diseases. Mitochondrial OGG1 plays a role in DNA repair and improved mitochondrial function. Overexpression of mitochondria-targeted OGG1 can reverse aging-associated inflammation and improve functions in mice. The release of mtDNA into the cytoplasm is regulated by mtOGG1, which controls age-associated inflammation.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Rongjun Zou, Jun Tao, Junxiong Qiu, Huimin Lu, Jianhua Wu, Hang Zhu, Ruibing Li, David Mui, Sam Toan, Xing Chang, Hao Zhou, Xiaoping Fan
Summary: This study aimed to elucidate the functional importance of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in sepsis-related multiple organ dysfunction syndrome (MODS). The results showed that deletion of DNA-PKcs improved mitochondrial function and attenuated organ damage in sepsis. Strategies targeting DNA-PKcs expression or activity may be valuable therapeutic options for preventing or reducing mitochondrial dysfunction and organ damage associated with sepsis-induced MODS.
JOURNAL OF ADVANCED RESEARCH
(2022)
Article
Neurosciences
Jana Hroudova, Tereza Novakova, Jan Korabecny, David Malinak, Lukas Gorecki, Zdenek Fisar
Summary: The trends in novel AD therapeutics are focused on multitarget-directed ligands, with certain compounds showing significant effects on mitochondrial enzyme activities. Some molecules appear to be suitable for further in vivo studies based on their balanced inhibitory effects on mitochondrial respiration and monoamine oxidase activity.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Toxicology
Zdenek Fisar, Kamil Musilek, Ondrej Benek, Lukas Hroch, Lucie Vinklarova, Monika Schmidt, Jana Hroudova, Jiri Raboch
Summary: Novel potential AD drugs were screened in vitro for their effects on mitochondrial enzymes, with six compounds showing minimal impact on mitochondrial respiratory rate and enzyme activity. Among them, AG18051 and one new compound demonstrated inhibition of MAO-B with minimal effects on mitochondrial respiration, making them promising candidates for further testing.
TOXICOLOGY LETTERS
(2021)
Article
Chemistry, Medicinal
Eva Mezeiova, Martina Hrabinova, Vendula Hepnarova, Daniel Jun, Jana Janockova, Lubica Muckova, Lukas Prchal, Zdena Kristofikova, Tomas Kucera, Lukas Gorecki, Katarina Chalupova, Jiri Kunes, Jana Hroudova, Ondrej Soukup, Jan Korabecny
Summary: Researchers prepared a family of huprineY-tryptophan heterodimers, which can inhibit cholinesterase and neuronal nitric oxide synthase enzymes, have an effect against A beta, and potentially can cross the blood-brain barrier. These heterodimers show promising pharmacological properties in AD and warrant further investigation.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Neurosciences
Matej L'uptak, Zdenek Fisar, Jana Hroudova
Summary: The study found that novel antipsychotics mainly decreased ATP production and increased ROS generation in mitochondria, but the inhibition of MAO-A may contribute to their antidepressant effect, while the MAO-B inhibition induced by brexpiprazole and loxapine may promote neuroplasticity and neuroprotection.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Psychiatry
Matej Luptak, Danica Michalickova, Zdenek Fisar, Eva Kitzlerova, Jana Hroudova
Summary: This review discusses the latest insights into the pathophysiology of and risk factors for schizophrenia, highlighting the key genetic features and current pharmacotherapy. It also mentions novel approaches and potential biomarkers in antipsychotic treatment. Preclinical and clinical studies have shown promising results for substances such as lumateperone, pimavanserin, and cannabidiol, indicating the possibility of expanding treatment options for schizophrenia.
WORLD JOURNAL OF PSYCHIATRY
(2021)
Article
Toxicology
Zdenek Fisar, Matej Luptak, Jana Hroudova
Summary: At high concentrations, RDV partially inhibits mitochondrial respiration complexes and MAO enzyme activity, but has minimal direct effect on mitochondrial respiration at therapeutic drug concentration.
TOXICOLOGY LETTERS
(2021)
Article
Physiology
Danica Michalickova, Hatice Kubra Ozturk, Jana Hroudova, Matej L'uptak, Tomas Kucera, Tomas Hrncir, Nikolina Kutinova Canova, Martin Sima, Ondrej Slanar
Summary: The aim of this study was to evaluate the therapeutic potential and mechanism of action of edaravone in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). The results showed that edaravone treatment ameliorated EAE severity, attenuated inflammation, decreased oxidative stress, increased the gene expression of Nrf2 and HO-1, increased the activity of the mitochondrial complex IV, and preserved ATP production in the spinal cords of EAE mice. These findings provide additional evidence of the potential of edaravone for the treatment of multiple sclerosis and expand our knowledge of its mechanism of action in the EAE model.
PHYSIOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Matej L'uptak, Zdenek Fisar, Jana Hroudova
Summary: This study evaluates and quantifies the effects of antidepressant drugs (agomelatine, ketamine and vortioxetine) on pig brain-isolated mitochondria in vitro. The results indicate that vortioxetine is the most potent inhibitor of mitochondrial complexes and complex I-linked respiration, while agomelatine and ketamine have inhibitory effects on specific complexes. Vortioxetine may activate an antioxidant mechanism, while agomelatine may contribute to oxidative damage and adverse effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Zdenek Fisar
Summary: The discovery of biomarkers and verification of biological hypotheses are crucial for understanding the etiology of schizophrenia. Risk factors and biomarkers can disrupt brain function and establish new homeostatic setpoints, leading to the symptoms of schizophrenia. Different risk factors and biomarkers can converge to cause the same symptoms, indicating the highly individual nature of the disease.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Review
Biochemistry & Molecular Biology
Zdenek Fisar
Summary: Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with A beta neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of A beta oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly A beta oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.
Article
Biochemistry & Molecular Biology
Matej L'uptak, Zdenek Fisar, Jana Hroudova
Summary: Mitochondrial dysfunction is involved in psychiatric and neurodegenerative disorders and can be used to predict treatment responsiveness. Understanding the mitochondrial effects of antidepressants is important to connect mitochondria with therapeutic and adverse effects.
Article
Biochemistry & Molecular Biology
Zdenek Fisar, Jana Hroudova, Martina Zverova, Roman Jirak, Jiri Raboch, Eva Kitzlerova
Summary: Mitochondrial dysfunction is a crucial cellular characteristic of aging and neurodegeneration, and platelets serve as a useful model to study its systemic manifestations. The age dependence of mitochondrial parameters was evaluated, and the impact of cognitive impairment was examined. The study found that mitochondrial enzyme activity and parameters of mitochondrial respiration showed a significant negative correlation with age, but there was no significant difference in age-related changes between individuals with and without cognitive impairment. These findings suggest that measuring mitochondrial respiration in intact platelets could be a potential means to assess age-related mitochondrial dysfunction.
