Article
Biochemistry & Molecular Biology
Sarah Thomas Broome, Alessandro Castorina
Summary: The study shows that buspirone has neuroprotective effects in models of Parkinson's disease, preventing damage to the central nervous system and improving mitochondrial function and antioxidant activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Rachel E. Hardy, Injae Chung, Yizhou Yu, Samantha H. Y. Loh, Nobuhiro Morone, Clement Soleilhavoup, Marco Travaglio, Riccardo Serreli, Lia Panman, Kelvin Cain, Judy Hirst, Luis M. Martins, Marion MacFarlane, Kenneth R. Pryde
Summary: Antipsychotic drugs, including the newer generation ones, can induce mitochondrial toxicity that leads to movement disorders. It is important to understand the underlying mechanisms to minimize these adverse effects.
Article
Biochemistry & Molecular Biology
Peiyu Xu, Sijie Huang, Chunyou Mao, Brian E. Krumm, X. Edward Zhou, Yangxia Tan, Xi-Ping Huang, Yongfeng Liu, Dan-Dan Shen, Yi Jiang, Xuekui Yu, Hualiang Jiang, Karsten Melcher, Bryan L. Roth, Xi Cheng, Yan Zhang, H. Eric Xu
Summary: The study reported two cryo-EM structures of human D3R in complex with an inhibitory G protein and bound to D3R-selective agonists PD128907 and pramipexole, revealing distinct agonist binding modes and conformational signatures for ligand-induced receptor activation, providing insights for designing specific ligands to treat CNS diseases targeting the dopaminergic system.
Article
Multidisciplinary Sciences
Susanne Prokop, Peter Abranyi-Balogh, Benjamin Barti, Marton Vamosi, Miklos Zoldi, Laszlo Barna, Gabriella M. Urban, Andras David Toth, Barna Dudok, Attila Egyed, Hui Deng, Gian Marco Leggio, Laszlo Hunyady, Mario van der Stelt, Gyorgy M. Keseru, Istvan Katona
Summary: The PharmacoSTORM single-molecule imaging technique combines fluorescent ligands and immunolabeling to provide a new approach for molecular pharmacology research at the cellular and subcellular levels, enabling precise quantification of drug-target interactions. By studying cariprazine binding to D3 dopamine receptors, the technique allows for accurate measurement of drug-target interactions and sheds light on its neurobiological substrate.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Kathryn Lanza, Christopher Bishop
Summary: Parkinson's Disease (PD) and long-term L-DOPA treatment induce plasticity that contributes to L-DOPA-induced dyskinesia (LID), with the dopamine D3 receptor (D3R) emerging as a promising target in LID management due to its upregulation in LID. D3R undergoes dynamic changes in both PD and LID, and recent genetic and pharmacologic tools have helped clarify its role in LID.
Review
Endocrinology & Metabolism
Claudia Pivonello, Roberta Patalano, Mariarosaria Negri, Rosa Pirchio, Annamaria Colao, Rosario Pivonello, Renata Simona Auriemma
Summary: Pituitary neuroendocrine tumors are a common type of intracranial tumor. Treatment with dopamine agonists can be effective, but resistance may occur in some patients.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Medicinal
Gui-Long Tian, Chia-Ju Hsieh, Michelle Taylor, Aladdin A. Riad, Robert R. Luedtke, Robert H. Mach
Summary: The difference in the secondary binding site between D2R and D3R has been utilized to design compounds with selectivity for D3R. This study prepared a series of bitopic ligands based on Fallypride to improve the selectivity for D3R using various secondary binding fragments. The results showed that compounds with a small alkyl group containing a heteroatom exhibited improved D3R selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Pramisha Adhikari, Bing Xie, Ana Semeano, Alessandro Bonifazi, Francisco O. Battiti, Amy H. Newman, Hideaki Yano, Lei Shi
Summary: The study focuses on developing D3R selective agonists over D2R and identifies compound AB04-88 with significant D3R selectivity and G protein bias. The chirality of the primary pharmacophore is key in conferring improved D3R potency, selectivity, and G protein signaling bias.
Article
Chemistry, Medicinal
Emma S. Gogarnoiu, Caleb D. Vogt, Julie Sanchez, Alessandro Bonifazi, Elizabeth Saab, Anver Basha Shaik, Omar Soler-Cedeno, Guo-Hua Bi, Benjamin Klein, Zheng-Xiong Xi, J. Robert Lane, Amy Hauck Newman
Summary: Highly selective dopamine D3 receptor (D3R) partial agonists/antagonists have not been successful for the treatment of psychostimulant use disorders (PSUD) due to low potency/efficacy or potential cardiotoxicity. This study suggests that moderately selective D3R/D2R partial agonists/antagonists may be effective in treating PSUD and comorbidities with other affective disorders. Cariprazine and its analogues showed promising results in reducing cocaine self-administration in rats.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Xiaoyan Ding, Mengdie Yang, Ning Wu, Jin Li, Rui Song
Summary: Abnormal fear memory can lead to stress disorders such as PTSD. Therefore, intervention in the formation of abnormal fear memory can be a new strategy for preventing and treating PTSD.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Medicinal
Radomir Juza, Iveta Vojtechova, Kristyna Stefkova-Mazochova, Wim Dehaen, Tomas Petrasek, Lukas Prchal, Tereza Kobrlova, Jiri Janousek, Premysl Vlcek, Eva Mezeiova, Daniel Svozil, Jana Zdarova Karasova, Jaroslav Pejchal, Holger Stark, Grzegorz J. Satala, Andrzej J. Bojarski, Monika Kubacka, Szczepan Mogilski, Alena Randakova, Kamil Musilek, Ondrej Soukup, Jan Korabecny
Summary: Schizophrenia is a serious mental disorder with an unknown pathomechanism. This study presents the design, synthesis, and evaluation of two promising compounds for the treatment of schizophrenia, which show potential in improving cognitive and negative symptoms.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Cristina Cosi, Jean-Claude Martel, Agnes L. Auclair, Ginetta Collo, Laura Cavalleri, Peter Heusler, Ludovic Leriche, Florence Gaudoux, Pierre Sokoloff, Paul C. Moser, Silvia Gatti-McArthur
Summary: F17464 is a new potential antipsychotic with a unique profile, showing high affinity for dopamine receptor subtype 3 and serotonin receptor subtype 1a, while having lower affinity for dopamine receptor subtype 2. It has demonstrated various neurochemistry and behavioral effects, suggesting therapeutic potential for schizophrenia and autism.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Psychiatry
Jan Kehr, Fu-Hua Wang, Fumio Ichinose, Shimako Yoshitake, Bence Farkas, Bela Kiss, Nika Adham
Summary: The study demonstrates that cariprazine has a preferential action on dopamine D-3 receptors, which may help improve cognitive deficits and negative/depressive symptoms in schizophrenia and related disorders. This drug has the ability to block the effects of D-3 receptor-preferring agonists on social behavior and neurochemistry.
FRONTIERS IN PSYCHIATRY
(2022)
Review
Biochemistry & Molecular Biology
Bela Kiss, Istvan Laszlovszky, Balazs Kramos, Andras Visegrady, Amrita Bobok, Gyorgy Levay, Balazs Lendvai, Viktor Roman
Summary: Dopamine D3 receptor plays a role in CNS functions and drug research, with efforts focused on finding high affinity ligands for potential treatment options in CNS diseases.
Article
Biochemistry & Molecular Biology
Boeun Lee, Michelle Taylor, Suzy A. Griffin, Tamara McInnis, Nathalie Sumien, Robert H. Mach, Robert R. Luedtke
Summary: The study showed that N-phenylpiperazine analogs can selectively bind to the human D3 dopamine receptor with significant D3 vs. D2 binding selectivity, potentially leading to the development of pharmacotherapeutics for levodopa-induced dyskinesia in patients with Parkinson's disease.
Article
Biochemistry & Molecular Biology
Veronica Zingales, Sebastiano Alfio Torrisi, Gian Marco Leggio, Claudio Bucolo, Filippo Drago, Salvatore Salomone
Summary: D3R stimulation in mouse aorta specifically induces vasoconstriction, while D2R stimulation does not. This is in line with the higher expression level of D3R in the aorta. Residual vasoconstriction elicited by high concentration D3R agonist in D3R(-)/(-) or in the presence of D3R antagonist is likely unrelated to dopamine receptors.
Article
Pharmacology & Pharmacy
Maria Consiglia Trotta, Carlo Gesualdo, Chiara Bianca Maria Platania, Domenico De Robertis, Mauro Giordano, Francesca Simonelli, Michele D'Amico, Filippo Drago, Claudio Bucolo, Settimio Rossi
Summary: This study identified five miRNAs associated with stages of diabetic retinopathy, validating them as potential prognostic biomarkers and pharmacological targets. Additionally, optical coherence tomography (OCT) assessment showed an increase in the number of hyperreflective spots (HRS) with worsening of DR stages.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Oriana Maria Maurel, Sebastiano Alfio Torrisi, Cristina Barbagallo, Michele Purrello, Salvatore Salomone, Filippo Drago, Marco Ragusa, Gian Marco Leggio
Summary: Our study found that the expression of miRNAs in different brain areas is associated with susceptibility/resilience to PTSD. Changes in specific miRNAs may influence the transcription levels of FKBP5 and BDNF, and show a linear correlation with stress-induced behavioral phenotypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Manuela Santonocito, Cristina Zappulla, Santa Viola, Luca Rosario La Rosa, Elena Solfato, Ilenia Abbate, Valeria Tarallo, Ivana Apicella, Chiara Bianca Maria Platania, Grazia Maugeri, Velia D'Agata, Claudio Bucolo, Sandro De Falco, Maria Grazia Mazzone, Francesco Giuliano
Summary: The study demonstrates that NaMESys-SOR eye drops can effectively deliver sorafenib to the retina and reduce proinflammatory and pro-angiogenic mediators in various animal models, showing potential for the treatment of proliferative retinopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Federica Conti, Francesca Lazzara, Giovanni Luca Romano, Chiara Bianca Maria Platania, Filippo Drago, Claudio Bucolo
Summary: Caffeine can alleviate retinal inflammation, restore retinal cell barrier function, and maintain normal levels of brain-derived neurotrophic factor (BDNF) in the retina. These findings suggest that caffeine is a good candidate for combating inflammation in retinal diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Instruments & Instrumentation
Elena Bellotti, Gabriella Contarini, Federica Geraci, Sebastiano Alfio Torrisi, Cateno Piazza, Filippo Drago, Gian Marco Leggio, Francesco Papaleo, Paolo Decuzzi
Summary: This study proposes the use of biodegradable microPlates for sustained release of risperidone to mitigate cognitive impairment in schizophrenia. The microPlates demonstrated slow release rates, and experiments on mice showed improved cognitive function with the use of risperidone microPlates compared to free risperidone. This suggests that risperidone-loaded microPlates are a promising platform for improving cognitive symptoms associated with schizophrenia.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Chaiara Bianca Maria Platania, Filippo Drago, Claudio Bucolo
Summary: The activation of P2X7 receptor is implicated in the pathophysiology of various retinal age-related diseases, making it a potential pharmacological target for preventing these devastating conditions.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Agnese Filippello, Stefania Di Mauro, Alessandra Scamporrino, Sebastiano Alfio Torrisi, Gian Marco Leggio, Antonino Di Pino, Roberto Scicali, Maurizio Di Marco, Roberta Malaguarnera, Francesco Purrello, Salvatore Piro
Summary: The dysfunctions of intestinal cells in obesity and associated diabetes may be related to impaired intestinal cell development. Lipotoxicity affects the differentiation of specific intestinal cell types, including enterocytes, goblet cells, and CCK cells. These findings provide new targets for obesity and diabetes therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Velia D'Agata, Agata Grazia D'Amico, Grazia Maugeri, Claudio Bucolo, Settimio Rossi, Salvatore Giunta
Summary: This study found that carnosol can protect retinal vascular endothelium from the damage caused by high glucose by activating the Nrf2/HO-1 signaling pathway. This suggests that carnosol may be a valuable drug for the treatment of diabetic retinopathy.
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
(2023)
Article
Nutrition & Dietetics
Justyna Godos, Marialaura Bonaccio, Wahidah H. Al-Qahtani, Wolfgang Marx, Melissa M. Lane, Gian Marco Leggio, Giuseppe Grosso
Summary: This study aimed to investigate the relationship between consumption of ultra-processed foods (UPFs) and depressive symptoms in younger Italian adults. The results showed that individuals with higher UPF consumption had a higher likelihood of having depressive symptoms. This association remained significant even after adjusting for potential confounding factors, indicating a potential link between UPF consumption and depressive symptoms in younger Italian individuals.
Article
Biochemistry & Molecular Biology
Martina Di Bartolomeo, Tibor Stark, Serena Di Martino, Fabio Arturo Iannotti, Jana Ruda-Kucerova, Giovanni Luca Romano, Martin Kuchar, Samuele Laudani, Petr Palivec, Fabiana Piscitelli, Carsten T. Wotjak, Claudio Bucolo, Filippo Drago, Vincenzo Di Marzo, Claudio D'Addario, Vincenzo Micale
Summary: Adolescent exposure to cannabinoids, such as THC, may increase the risk of psychosis in individuals exposed to perinatal insult. In this study, the researchers examined the effects of peripubertal THC exposure on rats that were also exposed to prenatal methylazoxymethanol acetate (MAM) or perinatal THC (pTHC). They found that the rats exposed to MAM or pTHC exhibited adult phenotypes relevant to schizophrenia, including social withdrawal and cognitive impairment. The researchers also observed changes in gene expression and DNA methylation, suggesting potential molecular mechanisms underlying these effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Veronica Rivi, Cristina Benatti, Joan M. C. Blom, Luca Pani, Nicoletta Brunello, Filippo Drago, Francesco Papaleo, Filippo Caraci, Federica Geraci, Sebastiano Alfio Torrisi, Gian Marco Leggio, Fabio Tascedda
Summary: Cognitive impairment in schizophrenia is a challenging problem that hasn't been solved clinically or pharmacologically. Dysfunctional dysbindin and dopamine receptor D3 have been found to improve cognitive functions, but the underlying molecular mechanisms are not fully understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Samuele Laudani, Justyna Godos, Federica Martina Di Domenico, Ignazio Barbagallo, Cinzia Lucia Randazzo, Gian Marco Leggio, Fabio Galvano, Giuseppe Grosso
Summary: Hypertension and cardiovascular disease are major global causes of death, and increased oxidative stress and inflammation are associated with endothelial dysfunction. Anthocyanins, with their antioxidant and cardioprotective effects, have garnered significant interest, but their detection in blood serum is limited due to metabolism by gut microbiota. This review summarizes the main findings from clinical studies on the cardioprotective effects of anthocyanins, as well as the role of gut microbiota in their metabolism, bioavailability, and impact on microbiota composition. Further research is needed to clarify which molecules and doses of anthocyanins offer vascular benefits, while considering the crucial role of the microbiota.
Article
Neurosciences
Sebastiano A. Torrisi, Silvia Rizzo, Samuele Laudani, Alessandro Ieraci, Filippo Drago, Gian Marco Leggio
Summary: Several studies have shown that chronic stress has a negative effect on recognition memory, but the effects of acute stress on this cognitive ability have not been well studied. This study aimed to investigate the impact of acute stress on recognition memory consolidation in a sex-dependent manner. The results showed that acute stress did not affect memory performance in male and female mice immediately after training, but it altered memory performance after a 24-hour delay, with sex-dependent effects.
NEUROBIOLOGY OF STRESS
(2023)
Article
Chemistry, Medicinal
Salvatore Giunta, Agata Grazia D'Amico, Grazia Maugeri, Claudio Bucolo, Giovanni Luca Romano, Settimio Rossi, Chiara M. Eandi, Elisabetta Pricoco, Velia D'Agata
Summary: In the area of drug discovery, repurposing strategies are used to discover new uses of approved drugs. In this study, the effects of DMF on early injury associated with diabetic retinopathy were investigated. The results showed that DMF can counteract the inflammatory process and the oxidative response in diabetic retinopathy.