@article{MTMT:34785746,
	title = {Non-canonical G protein signaling},
	url = {https://m2.mtmt.hu/api/publication/34785746},
	author = {Nuernberg, Bernd and -Hammer, Sandra Beer and Reisinger, Ellen and Leiss, Veronika},
	doi = {10.1016/j.pharmthera.2024.108589},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {255},
	unique-id = {34785746},
	issn = {0163-7258},
	abstract = {The original paradigm of classical - also referred to as canonical - cellular signal transduction of heterotrimeric G proteins (G protein) is defined by a hierarchical, orthograde interaction of three players: the agonist-activated G protein-coupled receptor (GPCR), which activates the transducing G protein, that in turn regulates its intracellular effectors. This receptor-transducer-effector concept was extended by the identification of regulators and adapters such as the regulators of G protein signaling (RGS), receptor kinases like BARK, or GPCR-interacting arrestin adapters that are integrated into this canonical signaling process at different levels to enable fine-tuning. Finally, the identification of atypical signaling mechanisms of classical regulators, together with the discovery of novel modulators, added a new and fascinating dimension to the cellular G protein signal transduction. This heterogeneous group of accessory G protein modulators was coined "activators of G protein signaling" (AGS) proteins and plays distinct roles in canonical and non-canonical G protein signaling pathways. AGS proteins contribute to the control of essential cellular functions such as cell development and division, intracellular transport processes, secretion, autophagy or cell movements. As such, they are involved in numerous biological processes that are crucial for diseases, like diabetes mellitus, cancer, and stroke, which represent major health burdens. Although the identification of a large number of non-canonical G protein signaling pathways has broadened the spectrum of this cellular communication system, their underlying mechanisms, functions, and biological effects are poorly understood. In this review, we highlight and discuss atypical G protein-dependent signaling mechanisms with a focus on inhibitory G proteins (Gi) involved in canonical and non-canonical signal transduction, review recent developments and open questions, address the potential of new approaches for targeted pharmacological interventions. (c) 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).},
	keywords = {COUPLED RECEPTORS; Cross-talk; GPCR; G protein; Biased signaling; HETEROTRIMERIC G-PROTEINS; ASYMMETRIC CELL-DIVISION; AGS protein; RECEPTOR-INDEPENDENT ACTIVATORS; ENERGY PHOSPHATE TRANSFER; PERTUSSIS-LIKE TOXIN; BETA-GAMMA DIMERS; KINASE NDPK B; G-ALPHA},
	year = {2024},
	eissn = {1879-016X}
}

@article{MTMT:34777781,
	title = {A novel therapeutic target for kidney diseases: Lessons learned from starvation response},
	url = {https://m2.mtmt.hu/api/publication/34777781},
	author = {Yamahara, K. and Yasuda-Yamahara, M. and Kume, S.},
	doi = {10.1016/j.pharmthera.2024.108590},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {254},
	unique-id = {34777781},
	issn = {0163-7258},
	year = {2024},
	eissn = {1879-016X}
}

@article{MTMT:34766123,
	title = {The role of microglia heterogeneity in synaptic plasticity and brain disorders: Will sequencing shed light on the discovery of new therapeutic targets?},
	url = {https://m2.mtmt.hu/api/publication/34766123},
	author = {You, Y. and Chen, Z. and Hu, W.-W.},
	doi = {10.1016/j.pharmthera.2024.108606},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {255},
	unique-id = {34766123},
	issn = {0163-7258},
	abstract = {Microglia play a crucial role in interacting with neuronal synapses and modulating synaptic plasticity. This function is particularly significant during postnatal development, as microglia are responsible for removing excessive synapses to prevent neurodevelopmental deficits. Dysregulation of microglial synaptic function has been well-documented in various pathological conditions, notably Alzheimer's disease and multiple sclerosis. The recent application of RNA sequencing has provided a powerful and unbiased means to decipher spatial and temporal microglial heterogeneity. By identifying microglia with varying gene expression profiles, researchers have defined multiple subgroups of microglia associated with specific pathological states, including disease-associated microglia, interferon-responsive microglia, proliferating microglia, and inflamed microglia in multiple sclerosis, among others. However, the functional roles of these distinct subgroups remain inadequately characterized. This review aims to refine our current understanding of the potential roles of heterogeneous microglia in regulating synaptic plasticity and their implications for various brain disorders, drawing from recent sequencing research and functional studies. This knowledge may aid in the identification of pathogenetic biomarkers and potential factors contributing to pathogenesis, shedding new light on the discovery of novel drug targets. The field of sequencing-based data mining is evolving toward a multi-omics approach. With advances in viral tools for precise microglial regulation and the development of brain organoid models, we are poised to elucidate the functional roles of microglial subgroups detected through sequencing analysis, ultimately identifying valuable therapeutic targets. © 2024 Elsevier Inc.},
	keywords = {Humans; NEURONS; metabolism; DEPRESSION; Pathogenesis; review; human; Sequencing; physiology; genetic risk; nonhuman; pathology; SYNAPTIC PLASTICITY; Aging; nerve cell; biological marker; Gene Expression; MULTIPLE SCLEROSIS; MULTIPLE SCLEROSIS; MULTIPLE SCLEROSIS; data mining; microglia; microglia; microglia; brain disease; nerve cell plasticity; nerve cell plasticity; Alzheimer disease; Alzheimer disease; Alzheimer disease; Genetic Heterogeneity; Genome-Wide Association Study; amyotrophic lateral sclerosis; morphological trait; Neuronal Plasticity; NEUROLOGICAL DISEASE; RNA sequencing; multiomics; cerebral organoid; Drug target discovery; microglia heterogeneity},
	year = {2024},
	eissn = {1879-016X}
}

@article{MTMT:34638580,
	title = {Retracing our steps: A review on autism research in children, its limitation and impending pharmacological interventions},
	url = {https://m2.mtmt.hu/api/publication/34638580},
	author = {Salloum-Asfar, Salam and Zawia, Nasser and Abdulla, Sara A.},
	doi = {10.1016/j.pharmthera.2023.108564},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {253},
	unique-id = {34638580},
	issn = {0163-7258},
	keywords = {autism; diagnostics; THERAPEUTICS; neurodevelopmental},
	year = {2024},
	eissn = {1879-016X}
}

@article{MTMT:34611544,
	title = {Therapeutic strategies to target connective tissue growth factor in fibrotic lung diseases},
	url = {https://m2.mtmt.hu/api/publication/34611544},
	author = {Isshiki, Takuma and Naiel, Safaa and Vierhout, Megan and Otsubo, Kohei and Ali, Pareesa and Tsubouchi, Kazuya and Yazdanshenas, Parichehr and Kumaran, Vaishnavi and Dvorkin-Gheva, Anna and Kolb, Martin R. J. and Ask, Kjetil},
	doi = {10.1016/j.pharmthera.2023.108578},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {253},
	unique-id = {34611544},
	issn = {0163-7258},
	abstract = {The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-beta. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach. (c) 2023 Elsevier Inc. All rights reserved.},
	keywords = {interstitial pneumonia; THERAPEUTICS; Pulmonary Fibrosis; CTGF; IPF},
	year = {2024},
	eissn = {1879-016X},
	orcid-numbers = {Ask, Kjetil/0000-0002-0202-735X}
}

@article{MTMT:34589146,
	title = {Organic cation transporters in psychiatric and substance use disorders},
	url = {https://m2.mtmt.hu/api/publication/34589146},
	author = {Honan, Lauren E. and Fraser-Spears, Rheaclare and Daws, Lynette C.},
	doi = {10.1016/j.pharmthera.2023.108574},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {253},
	unique-id = {34589146},
	issn = {0163-7258},
	abstract = {Psychiatric and substance use disorders inflict major public health burdens worldwide. Their widespread burden is compounded by a dearth of effective treatments, underscoring a dire need to uncover novel therapeutic targets. In this review, we summarize the literature implicating organic cation transporters (OCTs), including three subtypes of OCTs (OCT1, OCT2, and OCT3) and the plasma membrane monoamine transporter (PMAT), in the neurobiology of psychiatric and substance use disorders with an emphasis on mood and anxiety disorders, alcohol use disorder, and psychostimulant use disorder. OCTs transport monoamines with a low affinity but high capacity, situating them to play a central role in regulating monoamine homeostasis. Preclinical evidence discussed here suggests that OCTs may serve as promising targets for treatment of psychiatric and substance use disorders and encourage future research into their therapeutic potential.(c) 2023 Published by Elsevier Inc.},
	keywords = {Dopamine; SEROTONIN; Psychiatric disorders; SUBSTANCE USE DISORDERS; MONOAMINE TRANSPORTERS; Organic cation transporters},
	year = {2024},
	eissn = {1879-016X}
}

@article{MTMT:34585655,
	title = {Therapeutic potential of stem cells in regeneration of liver in chronic liver diseases: Current perspectives and future challenges},
	url = {https://m2.mtmt.hu/api/publication/34585655},
	author = {Yadav, Poonam and Singh, Sumeet Kumar and Rajput, Sonu and Allawadhi, Prince and Khurana, Amit and Weiskirchen, Ralf and Navik, Umashanker},
	doi = {10.1016/j.pharmthera.2023.108563},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {253},
	unique-id = {34585655},
	issn = {0163-7258},
	abstract = {The deposition of extracellular matrix and hyperplasia of connective tissue characterizes chronic liver disease called hepatic fibrosis. Progression of hepatic fibrosis may lead to hepatocellular carcinoma. At this stage, only liver transplantation is a viable option. However, the number of possible liver donors is less than the number of patients needing transplantation. Consequently, alternative cell therapies based on non-stem cells (e.g., fibroblasts, chondrocytes, keratinocytes, and hepatocytes) therapy may be able to postpone hepatic disease, but they are often ineffective. Thus, novel stem cell-based therapeutics might be potentially important cutting-edge approaches for treating liver diseases and reducing patient' suffering. Several signaling pathways provide targets for stem cell interventions. These include pathways such as TGF-beta, STAT3/BCL-2, NADPH oxidase, Raf/MEK/ ERK, Notch, and Wnt/beta-catenin. Moreover, mesenchymal stem cells (MSCs) stimulate interleukin (IL)-10, which inhibits T-cells and converts M1 macrophages into M2 macrophages, producing an anti-inflammatory environment. Furthermore, it inhibits the action of CD4+ and CD8+ T cells and reduces the activity of TNF-alpha and interferon cytokines by enhancing IL-4 synthesis. Consequently, the immunomodulatory and antiinflammatory capabilities of MSCs make them an attractive therapeutic approach. Importantly, MSCs can inhibit the activation of hepatic stellate cells, causing their apoptosis and subsequent promotion of hepatocyte proliferation, thereby replacing dead hepatocytes and reducing liver fibrosis. This review discusses the multidimensional therapeutic role of stem cells as cell-based therapeutics in liver fibrosis.},
	keywords = {IMMUNOMODULATION; liver fibrosis; Mesenchymal Stem Cells; Chronic liver diseases},
	year = {2024},
	eissn = {1879-016X},
	orcid-numbers = {Weiskirchen, Ralf/0000-0003-3888-0931}
}

@article{MTMT:34535454,
	title = {Recent drug design strategies and identification of key heterocyclic scaffolds for promising anticancer targets},
	url = {https://m2.mtmt.hu/api/publication/34535454},
	author = {Mushtaq, A. and Wu, P. and Naseer, M.M.},
	doi = {10.1016/j.pharmthera.2023.108579},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {254},
	unique-id = {34535454},
	issn = {0163-7258},
	abstract = {Cancer, a noncommunicable disease, is the leading cause of mortality worldwide and is anticipated to rise by 75% in the next two decades, reaching approximately 25 million cases. Traditional cancer treatments, such as radiotherapy and surgery, have shown limited success in reducing cancer incidence. As a result, the focus of cancer chemotherapy has switched to the development of novel small molecule antitumor agents as an alternate strategy for combating and managing cancer rates. Heterocyclic compounds are such agents that bind to specific residues in target proteins, inhibiting their function and potentially providing cancer treatment. This review focuses on privileged heterocyclic pharmacophores with potent activity against carbonic anhydrases and kinases, which are important anticancer targets. Evaluation of ongoing pre-clinical and clinical research of heterocyclic compounds with potential therapeutic value against a variety of malignancies as well as the provision of a concise summary of the role of heterocyclic scaffolds in various chemotherapy protocols have also been discussed. The main objective of the article is to highlight key heterocyclic scaffolds involved in recent anticancer drug design that demands further attention from the drug development community to find more effective and safer targeted small-molecule anticancer agents. © 2023 Elsevier Inc.},
	keywords = {PHARMACOLOGY; DRUG DESIGN; Carbonic Anhydrases; Cancer treatment; Kinases; Heterocyclic; targeted anticancer drugs},
	year = {2024},
	eissn = {1879-016X}
}

@article{MTMT:34493845,
	title = {Repurposing of pexidartinib for microglia depletion and renewal},
	url = {https://m2.mtmt.hu/api/publication/34493845},
	author = {Weyer, M.-P. and Strehle, J. and Schäfer, M.K.E. and Tegeder, I.},
	doi = {10.1016/j.pharmthera.2023.108565},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {253},
	unique-id = {34493845},
	issn = {0163-7258},
	abstract = {Pexidartinib (PLX3397) is a small molecule receptor tyrosine kinase inhibitor of colony stimulating factor 1 receptor (CSF1R) with moderate selectivity over other members of the platelet derived growth factor receptor family. It is approved for treatment of tenosynovial giant cell tumors (TGCT). CSF1R is highly expressed by microglia, which are macrophages of the central nervous system (CNS) that defend the CNS against injury and pathogens and contribute to synapse development and plasticity. Challenged by pathogens, apoptotic cells, debris, or inflammatory molecules they adopt a responsive state to propagate the inflammation and eventually return to a homeostatic state. The phenotypic switch may fail, and disease-associated microglia contribute to the pathophysiology in neurodegenerative or neuropsychiatric diseases or long-lasting detrimental brain inflammation after brain, spinal cord or nerve injury or ischemia/hemorrhage. Microglia also contribute to the growth permissive tumor microenvironment of glioblastoma (GBM). In rodents, continuous treatment for 1–2 weeks via pexidartinib food pellets leads to a depletion of microglia and subsequent repopulation from the remaining fraction, which is aided by peripheral monocytes that search empty niches for engraftment. The putative therapeutic benefit of such microglia depletion or forced renewal has been assessed in almost any rodent model of CNS disease or injury or GBM with heterogeneous outcomes, but a tendency of partial beneficial effects. So far, microglia monitoring e.g. via positron emission imaging is not standard of care for patients receiving Pexidartinib (e.g. for TGCT), so that the depletion and repopulation efficiency in humans is still largely unknown. Considering the virtuous functions of microglia, continuous depletion is likely no therapeutic option but short-lasting transient partial depletion to stimulate microglia renewal or replace microglia in genetic disease in combination with e.g. stem cell transplantation or as part of a multimodal concept in treatment of glioblastoma appears feasible. The present review provides an overview of the preclinical evidence pro and contra microglia depletion as a therapeutic approach. © 2023 Elsevier Inc.},
	keywords = {PAIN; microglia; mental disease; RECEPTOR TYROSINE KINASE; glioblastoma; brain injury; NEURODEGENERATIVE DISEASE; Colony stimulating factor 1 receptor},
	year = {2024},
	eissn = {1879-016X}
}

@article{MTMT:34626085,
	title = {NLRP3 and cancer: Pathogenesis and therapeutic opportunities},
	url = {https://m2.mtmt.hu/api/publication/34626085},
	author = {Tengesdal, Isak W. and Dinarello, Charles A. and Marchetti, Carlo},
	doi = {10.1016/j.pharmthera.2023.108545},
	journal-iso = {PHARMACOL THERAPEUT},
	journal = {PHARMACOLOGY & THERAPEUTICS},
	volume = {251},
	unique-id = {34626085},
	issn = {0163-7258},
	keywords = {CASPASE-1; Tumor microenvironment; Pyroptosis; NLRP3; response to therapy; IL-1 family},
	year = {2023},
	eissn = {1879-016X}
}