Review
Nutrition & Dietetics
Fahimeh Martami, Kathleen F. Holton
Summary: Glutamate plays a significant role in migraines, with excessive levels contributing to excitotoxicity and neuronal injury. Certain nutrients have protective effects against excitotoxicity and can restore glutamate homeostasis.
Review
Biochemistry & Molecular Biology
Francesca Provenzano, Carola Torazza, Tiziana Bonifacino, Giambattista Bonanno, Marco Milanese
Summary: In the last two decades, increasing evidence has shown the active contribution of non-neuronal cells to neurodegenerative disorders. Among glial cells, astrocytes play a crucial role in driving the progression of amyotrophic lateral sclerosis (ALS) through various pathological mechanisms, such as neuroinflammation, mitochondrial dysfunction, oxidative stress, energy metabolism impairment, and altered release of miRNAs, extracellular vesicles, and neurotrophic factors. This review focuses on the specific role of ALS astrocytes in glutamate excitotoxicity, highlighting the molecular mechanisms by which astrocytes contribute to the increase in extracellular glutamate levels and also experience the toxic effects of excessive glutamate. The review also identifies knowledge gaps that warrant further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Aman B. Upaganlawar, Nitu L. Wankhede, Mayur B. Kale, Mohit D. Umare, Aayush Sehgal, Sukhbir Singh, Saurabh Bhatia, Ahmed Al-Harrasi, Agnieszka Najda, Renata Nurzynska-Wierdak, Simona Bungau, Tapan Behl
Summary: Epilepsy, affecting nearly 50 million people worldwide, can be caused by genetic predisposition or acquired acute insult leading to alteration of cellular and molecular mechanisms. The imbalanced state of enhanced excitatory glutamatergic and reduced inhibitory GABAergic signaling is considered to be accountable for seizures associated damage. Neurodegeneration contributing to epileptogenesis has become increasingly appreciated, with potential intervention through vitamin E therapy in managing epilepsy.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Neurosciences
Maryam N. Al-Nasser, Ian R. Mellor, Wayne G. Carter
Summary: This study systematically reviewed the effects of L-Glu on neurodegenerative diseases and found that aberrant accumulation of L-Glu may lead to multiple pathogenic mechanisms that influence neuronal viability. Further clinical and epidemiological studies are needed due to the limitations of the existing research.
Article
Biochemistry & Molecular Biology
Ting Zuo, Bingzheng Gong, Yang Gao, Liangjie Yuan
Summary: This study aimed to investigate the stimulating effects of glutamate on astrocytes and the concentration range of glutamate transportable by astrocytes. The results showed that high concentrations of glutamate can activate astrocytes and promote the production of pro-inflammatory factors, and the concentration range of glutamate transported by astrocytes is approximately less than 50-100 μM. Therefore, experimental antagonization of glutamate excitotoxicity is feasible.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Medicine, Research & Experimental
Shirui Dai, Chao Wang, Cheng Zhang, Lemeng Feng, Wulong Zhang, Ye He, Xuezhi Zhou, Xiaobo Xia, Baihua Chen, Weitao Song
Summary: The study found that tBHQ has a protective effect on retinal damage caused by glutamate excitotoxicity. By regulating cellular oxidative stress and apoptosis pathways, tBHQ can reduce cell damage induced by glutamate.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Neurosciences
Daniel Pukoli, Helga Polyak, Cecilia Rajda, Laszlo Vecsei
Summary: The kynurenine pathway is involved in the pathogenesis of multiple sclerosis, with dysregulation and upregulated levels contributing to neuro-axonal damage and degeneration. Neurofilaments serve as reliable biomarkers for neuro-axonal damage severity and treatment response in multiple sclerosis. There is increasing evidence of a connection between molecules in the kynurenine metabolic pathway and changes in neurofilament concentrations, suggesting its potential as an important biomarker for disease progression.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Oh Yun Kwon, Seung Ho Lee
Summary: The study demonstrated that Ishige okamurae extract could attenuate neurodegenerative processes by regulating MAPKs/Nrf-2/HO-1 antioxidant pathways, inhibiting neuronal dysregulation induced by TMT and glutamate.
Review
Geriatrics & Gerontology
Farida El Gaamouch, Fiona Chen, Lap Ho, Hsiao-Yun Lin, Chongzhen Yuan, Jean Wong, Jun Wang
Summary: Alzheimer's disease is an irreversible neurodegenerative disease that affects millions of people worldwide. Despite the lack of a cure, dietary and nutrition factors have shown potential in delaying the onset and progression of the disease.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Pharmacology & Pharmacy
Bayan Sailike, Zhannur Omarova, Janar Jenis, Altynay Adilbayev, Burkitkan Akbay, Sholpan Askarova, Wei-Lin Jin, Tursonjan Tokay
Summary: This review gathers detailed information on the neuroprotective and antiepileptic properties of the genus Artemisia and its potential underlying mechanisms. The extracts from Artemisia species possess antioxidant, anti-inflammatory, anti-apoptotic, anticonvulsant, and pro-cognitive properties, possibly through modulation of mitochondrial ROS production, upregulation of receptor activities, and interference with anti-inflammatory and anti-apoptotic signaling pathways.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Kathleen F. Holton
Summary: This article discusses how excitotoxicity, oxidative stress, and neuroinflammation interact to form a neurotoxic triad, and how specific dietary micronutrients can protect against them. Future dietary interventions may focus on the effects on all three aspects of the neurotoxic triad.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Environmental Sciences
Ali H. Abu Almaaty, Rehab M. Mosaad, Mohamed K. Hassan, Elham H. A. Ali, Ghada A. Mahmoud, Hassan Ahmed, Nahla Anber, Saad Alkahtani, Mohamed M. Abdel-Daim, Lotfi Aleya, Seddik Hammad
Summary: The study evaluated the therapeutic effects of Urtica dioica extracts on memory dysfunction, amnesia, and oxidative stress induced by scopolamine. The results demonstrated that Urtica dioica extracts, particularly nettle root, significantly improved memory deficits and monoamine levels, showing antioxidative stress effects.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Daniel Pukoli, Laszlo Vecsei, Bruno Bonetti
Summary: Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS). Neurodegeneration begins with acute lymphocytic inflammation and may progress to chronic inflammation. Chronic inflammation is associated with the development of smouldering lesions, which are characterized by continuous low-grade demyelination and neurodegeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Na Ji, Mengzhu Lei, Yating Chen, Shaowen Tian, Chuanyu Li, Bo Zhang
Summary: Depression is a social problem that affects a large number of people worldwide, requiring prompt attention and management. Accumulating research has revealed the importance of monoamine deficiency in depression pathogenesis, leading to the development of antidepressants that target the monoamine system. However, these antidepressants have drawbacks such as slow action and treatment resistance, highlighting the need to explore novel pathogenesis for more effective therapeutic methods.
Article
Immunology
Suliman Y. Alomar, Bassant M. Barakat, Mohamed Eldosoky, Hoda Atef, Abdelaty Shawky Mohamed, Reda Elhawary, Mohamed El-Shafey, Amal M. Youssef, Amany Y. Elkazaz, Attia M. Gabr, Abdelhakeem A. Elaskary, Mohamed A. K. Salih, Sultan Othman Alolayan, Sawsan A. Zaitone
Summary: MET treatment significantly reduced oxidative stress levels in the retina, suppressed inflammation, glutamate excitotoxicity, and the increase in vascular endothelial growth factor induced by diabetes. Additionally, MET also reduced the gene expression of NFκB, tumor necrosis factor-α, and TLR4 in diabetic rats.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Neurosciences
Fanni Annamaria Boros, Laszlo Vecsei, Peter Klivenyi
Summary: Parkinson's disease is the second most common neurodegenerative disease globally, and there is a need to identify biomarkers and new therapeutic targets. NEAT1 has emerged as a possible regulatory hub in PD development, but its exact role is still debated. The contradictory findings of NEAT1's involvement in PD highlight the complexity of neurodegenerative disorders and the limitations of disease models, calling for further research to clarify its potential as a biomarker and therapeutic target.
JOURNAL OF PARKINSONS DISEASE
(2021)
Article
Pharmacology & Pharmacy
Kinga Molnar, Balint Lorinczi, Csilla Fazakas, Istvan Szatmari, Ferenc Fulop, Noemi Kmetyko, Robert Berkecz, Istvan Ilisz, Istvan A. Krizbai, Imola Wilhelm, Laszlo Vecsei
Summary: The study synthesized six novel aminoalkylated amide derivatives of kynurenic acid, with SZR-104 showing the highest permeability through the blood-brain barrier. Compared to kynurenic acid, xanthurenic acid, and 39B, SZR-104 demonstrated significantly higher penetrability and potential to inhibit epileptiform activity in the brain.
Article
Clinical Neurology
Katalin Despotov, Denes Zadori, Gabor Veres, Katalin Jakab, Gabriella Gardian, Eszter Toth, Tamas Zsigmond Kincses, Laszlo Vecsei, Andras Ajtay, Daniel Bereczki, Peter Klivenyi
Summary: This study described the characteristics of Hungarian HD patients and mutation carriers, finding that the genetic and clinical features of this population were consistent with previous Hungarian studies and international literature, with the exception of a higher ratio of reduced penetrance and intermediate alleles.
Article
Clinical Neurology
Krisztian Kocsis, Nikoletta Szabo, Eszter Toth, Andras Kiraly, Peter Farago, Balint Kincses, Daniel Vereb, Bence Bozsik, Katalin Boross, Melinda Katona, Peter Bodnar, Nyul Gabor Laszlo, Laszlo Vecsei, Peter Klivenyi, Krisztina Bencsik, Zsigmond Tamas Kincses
Summary: This study demonstrates that black holes can be separated into two distinct clusters based on their intensity values on various sequences, only one of which is related to clinical parameters. It emphasizes the joint role of FSPGR and SE sequences in monitoring MS patients and provides insight into the role of black holes in MS.
FRONTIERS IN NEUROLOGY
(2021)
Article
Pharmacology & Pharmacy
Mohammad Al-Mandi Al-Karagholi, Jakob Moller Hansen, Dalia Abou-Kassem, Anna Koldbro Hansted, Kumari Ubhayasekera, Jonas Bergquist, Laszlo Vecsei, Inger Jansen-Olesen, Messoud Ashina
Summary: The kynurenine pathway is a potential drug discovery target in neuroscience, with L-kynurenine emerging as a prodrug targeting glutamate receptors. LKYN was found to be safe and well-tolerated in humans at various dose levels, with no significant vascular effects observed after infusion. Further exploration of LKYN's therapeutic potential in stroke and epilepsy in human studies is warranted.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2021)
Article
Pharmacology & Pharmacy
Masaru Tanaka, Nora Torok, Laszlo Vecsei
EXPERT OPINION ON PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Viktoria Kovacs, Gabor Remzso, Timea Kormoczi, Robert Berkecz, Valeria Toth-Szuki, Andrea Penzes, Laszlo Vecsei, Ferenc Domoki
Summary: The study investigated the potential neuroprotective effects of the KYNA analog SZR72 in piglets with HIE. While SZR72 enhanced neuronal activity and EEG recovery, it did not ameliorate early neuronal damage post-asphyxia. In comparison, hypothermia treatment showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Daniel Sandi, Zsanett Fricska-Nagy, Krisztina Bencsik, Laszlo Vecsei
Summary: Neurodegeneration plays a crucial role in the pathogenesis of multiple sclerosis, leading to progression, pathopsychological disturbances, and optic neuropathy. The kynurenine pathway has been highlighted as a potential therapeutic target for neuroprotective drugs in MS, with promising data emerging from clinical evaluations. Further research on the pathway is expected to provide concrete results for everyday medicine in the future.
Editorial Material
Medicine, Research & Experimental
Masaru Tanaka, Laszlo Vecsei
Summary: The tryptophan-kynurenine metabolic pathway is crucial in producing endogenous bioactive molecules, and its activation is linked to the pathogenesis of various diseases. Efforts have been made to calibrate the levels and ratios of kynurenines to identify biomarkers and diagnostic targets. This editorial discusses the interaction between biosystems and the kynurenine system, as well as potential measures to evaluate stress levels that may lead to illnesses.
ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Rita Maszlag-Torok, Fanni A. Boros, Laszlo Vecsei, Peter Klivenyi
Summary: This study investigated the potential association of SIRT1, -2, and -6 gene polymorphisms with the risk of Parkinson's disease (PD) in the Hungarian population. It found that certain SNPs in SIRT1 and SIRT6 were weakly associated with PD risk, while SNPs in SIRT2 showed no association. Additionally, mRNA levels of SIRT1 were down-regulated, SIRT6 were up-regulated, and SIRT2 remained unchanged in PD patients compared to controls, suggesting a potential role of SIRT1 and SIRT6 in the pathogenesis of PD.
SCIENTIFIC REPORTS
(2021)
Review
Neurosciences
Daniel Pukoli, Helga Polyak, Cecilia Rajda, Laszlo Vecsei
Summary: The kynurenine pathway is involved in the pathogenesis of multiple sclerosis, with dysregulation and upregulated levels contributing to neuro-axonal damage and degeneration. Neurofilaments serve as reliable biomarkers for neuro-axonal damage severity and treatment response in multiple sclerosis. There is increasing evidence of a connection between molecules in the kynurenine metabolic pathway and changes in neurofilament concentrations, suggesting its potential as an important biomarker for disease progression.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Immunology
Marietta Z. Poles, Anna Naszai, Levente Gulacsi, Balint L. Czako, Krisztian G. Gal, Romy J. Glenz, Dishana Dookhun, Attila Rutai, Szabolcs P. Tallosy, Andrea Szabo, Balint Lorinczi, Istvan Szatmari, Ferenc Fulop, Laszlo Vecsei, Mihaly Boros, Laszlo Juhasz, Jozsef Kaszaki
Summary: KYNA and its synthetic analogues have been found to be potential neuroprotective agents in sepsis by reducing peripheral formation of NETs, lowering BBB permeability changes, and alleviating mitochondrial dysfunction in the CNS.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Neurosciences
Janos Tajti, Delia Szok, Aliz Nyari, Laszlo Vecsei
Summary: This review summarizes the significant breakthroughs in migraine research made by headache scientists in the past 40 years, including the pathogenesis and treatment options for migraine. The theory of the trigeminovascular system has played a crucial role in this field, and the calcitonin gene-related peptide has become an important target for the treatment of migraine. The related studies have provided a solid foundation and treatment strategies in both preclinical and clinical settings.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2022)
Review
Clinical Neurology
Masaru Tanaka, Eleonora Spekker, Agnes Szabo, Helga Polyak, Laszlo Vecsei
Summary: The neurodevelopmental theory suggests that disruptions in brain development can lead to subsequent neuropsychiatric symptoms. Preclinical studies have shown that neurodevelopmental pathology plays a role in various psychiatric disorders and neurodegenerative diseases.
JOURNAL OF NEURAL TRANSMISSION
(2022)
Article
Multidisciplinary Sciences
Helga Polyak, Edina Katalin Cseh, Zsuzsanna Bohar, Cecilia Rajda, Denes Zadori, Peter Klivenyi, Jozsef Toldi, Laszlo Vecsei
Summary: The study aimed to measure the metabolites of the KP in CPZ treated animals, with a focus on KYNA levels. Results showed a marked reduction of KYNA in the demyelinating phase, suggesting a potential involvement of the KP in the pathomechanism of MS in a non-immune mediated model.