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.
Article
Biochemistry & Molecular Biology
Tung-Tai Kuo, Yuan-Hao Chen, Vicki Wang, Eagle Yi-Kung Huang, Kuo-Hsing Ma, Nigel H. H. Greig, Jin Jung, Ho- Choi, Lars Olson, Barry J. J. Hoffer, Kuan-Yin Tseng
Summary: This study evaluated the efficacy of PT320 on L-DOPA-induced dyskinetic behaviors and neurochemistry in a progressive Parkinson's disease MitoPark mouse model. The results showed that early administration of PT320 significantly reduced the severity of L-DOPA-induced abnormal involuntary movements, particularly in excessive standing and abnormal paw movements. However, late administration of PT320 did not improve any L-DOPA-induced dyskinesia measurements. Furthermore, early treatment with PT320 increased both tonic and phasic release of dopamine in striatal slices, indicating its potential role in alleviating L-DOPA-induced dyskinesia in Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Clinical Neurology
Kaitlyn M. L. Cramb, Dayne Beccano-Kelly, Stephanie J. Cragg, Richard Wade-Martins
Summary: Cramb et al. provide a review of evidence suggesting dopamine release deficits occur prior to neurodegeneration in Parkinson's disease. They also highlight the need for further investigation in understanding the mechanisms behind these deficits.
Review
Clinical Neurology
Carissa A. Hansen, Douglas R. Miller, Stephanie Annarumma, Carley T. Rusch, Adolfo Ramirez-Zamora, Habibeh Khoshbouei
Summary: This manuscript provides a comprehensive review of treatment protocols, absorption, distribution, and drug/food interactions related to L-DOPA-induced dyskinesia, and discusses current strategies and future directions.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Waijiao Cai, Kazumasa Wakamatsu, Fabio A. Zucca, Qing Wang, Kai Yang, Niyaz Mohamadzadehonarvar, Pranay Srivastava, Hitomi Tanaka, Gabriel Holly, Luigi Casella, Shosuke Ito, Luigi Zecca, Xiqun Chen
Summary: By studying samples of substantia nigra from patients with Parkinson's disease, we found increased ratios of pheomelanin to dopamine in the melanin content, as well as reduced levels of eumelanins derived from both DOPA and dopamine. Additionally, an increase in pheomelanin relative to dopamine pheomelanin was observed in Parkinson's disease. These findings provide insights into the roles of pheomelanin and eumelanin in the pathophysiology of Parkinson's disease.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Jose A. Pineda-Pardo, Alvaro Sanchez-Ferro, Mariana H. G. Monje, Nicola Pavese, Jose A. Obeso
Summary: The striatal dopaminergic deficit in Parkinson's disease follows a somatotopically related pattern, with an upper-limb onset and progression to other regions of the striatum. The denervation of the putamen was confirmed in both hemispheres and corresponding hemibodies. The findings suggest a precise somatotopic onset of nigrostriatal denervation in Parkinson's disease.
Article
Biochemistry & Molecular Biology
Vladimir M. Pogorelov, Michael L. Martini, Jian Jin, William C. Wetsel, Marc G. Caron
Summary: L-DOPA is the main treatment for Parkinson's disease, but it can lead to dyskinesia over time. In this study, dopamine-depleted dopamine-transporter KO (DDD) mice were used as an acute PD model to screen novel compounds for anti-parkinsonian and L-DOPA-induced dyskinesia. The researchers found that oral stereotypies could be used as an index for LID in DDD mice.
Article
Clinical Neurology
James A. Brissenden, Teresa Scerbak, Roger L. Albin, Taraz G. Lee
Summary: This study aims to differentiate between the short-duration response (SDR) and long-duration response (LDR), and the results show that both SDR and LDR induced by dopamine replacement therapy can significantly improve motor performance, indicating that bradykinesia is not solely due to deficient modulation of motivational processes.
MOVEMENT DISORDERS
(2023)
Article
Geriatrics & Gerontology
Hiromi Sano, Atsushi Nambu
Summary: ZNS is an anticonvulsant drug that has beneficial effects on Parkinson's disease and its side effect, L-DOPA-induced dyskinesia, but can also have adverse effects.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Feras Altwal, Fernando E. Padovan-Neto, Alexandra Ritger, Heinz Steiner, Anthony R. West
Summary: Research has shown that vilazodone may reduce dyskinesia in patients with Parkinson's disease without interfering with the prokinetic effects of L-DOPA, possibly through its action on 5-HT receptors.
Review
Biochemistry & Molecular Biology
Srijan Acharya, Kyeong-Man Kim
Summary: The review discusses the interaction between the brain dopaminergic and cholinergic systems in the pathogenesis and treatment of schizophrenia and Parkinson's disease, including their roles in motor plan selection, negative symptoms, and nicotine-induced protection of DAergic neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Chia-Wen Chang, Yu-Hsuan Lin, Cheng-Han Tsai, Sivasankar Kulandaivel, Yi-Chun Yeh
Summary: A novel heat-stable enzyme was developed for a protein-and cell-based biosensor, enabling the detection of L-DOPA for the first time. The detection of L-DOPA was achieved through a red fluorescent signal within 30 minutes. Furthermore, a sequential analysis method using dual-fluorescent signals was developed for the sensitive detection of dopamine and L-DOPA coexistence, allowing for monitoring of the therapy for Parkinson's disease patients treated with L-DOPA.
ANALYTICA CHIMICA ACTA
(2022)
Article
Neurosciences
Riccardo Viaro, Francesco Longo, Fabrizio Vincenzi, Katia Varani, Michele Morari
Summary: Previous studies have demonstrated that L-DOPA can enhance dopamine release through SCH23390-sensitive D1 receptors and potentially promote dopamine efflux via conversion to dopamine and reversal of the DA transporter.
Article
Neurosciences
Zhihua Liu, Aijuan Yan, Jiahao Zhao, Shuyuan Yang, Lu Song, Zhenguo Liu
Summary: The study revealed the important role of p75NTR in patients with Parkinson's disease and suggested it as a new target for managing L-dopa-induced dyskinesia.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rupsha Mondal, Chayan Banerjee, Sumangal Nandy, Moumita Roy, Joy Chakraborty
Summary: Parkinson's disease (PD) is a prevalent neuro-motor disorder caused by progressive loss of dopamine neurons in the brain. L-DOPA therapy, a precursor for dopamine synthesis, is commonly used to manage PD-associated behavioral dysfunctions. However, excessive dopamine can potentiate neurotoxicity, highlighting the need to minimize dopamine toxicity during therapy. In this study, it is found that inhibiting the Calcineurin (CaN)-DRP1 axis can protect cells from dopamine toxicity and improve behavioral outcomes in a mice model of PD. CaN inhibitors may enhance the therapeutic efficacy of L-DOPA treatment.
CELL AND BIOSCIENCE
(2023)
Article
Chemistry, Medicinal
Gianfabio Giorgioni, Fabio Del Bello, Wilma Quaglia, Luca Botticelli, Carlo Cifani, E. Micioni Di Bonaventura, M. V. Micioni Di Bonaventura, Alessandro Piergentili
Summary: This article discusses the role of ghrelin and its receptor GHS-R1a in multiple physiological processes and their potential in treating various disorders. It also introduces the development of nonpeptide small molecules as GHS-R1a agonists, antagonists, and inverse agonists in recent years, as well as the pharmacological effects of the most studied ligands.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Cecilia Baldassarri, Gianfabio Giorgioni, Alessandro Piergentili, Wilma Quaglia, Stefano Fontana, Valerio Mammoli, Gabriele Minazzato, Elisa Marangoni, Massimiliano Gasparrini, Leonardo Sorci, Nadia Raffaelli, Loredana Cappellacci, Riccardo Petrelli, Fabio Del Bello
Summary: The inhibition of NAD biosynthesis is a potential therapeutic approach against cancer, while boosting NAD biosynthesis is relevant for neurodegeneration and metabolic diseases. Targeting NAMPT and NAPRT enzymes that regulate NAD biosynthesis has shown promise. In this study, new NAPRT modulators were identified as potential activators or inhibitors, with compound 18 showing good pharmacokinetic properties and behaving as an inhibitor towards NA and PRPP. Docking studies were performed to understand the structural basis, and a preliminary pharmacophore model shed light on the transition from inhibitors to activators.
Article
Biochemistry & Molecular Biology
Emira D'Amico, Tania Vanessa Pierfelice, Rosa Amoroso, Ivana Cacciatore, Camillo D'Arcangelo, Stefania Lepore, Simonetta D'Ercole, Natalia Di Pietro, Annalisa Di Rienzo, Morena Petrini, Adriano Piattelli, Alessia Ricci, Susi Zara, Antonio Di Stefano, Giovanna Iezzi, Barbara De Filippis
Summary: Recently, research has focused on finding new approaches to manage oral wound healing. The use of resveratrol (RSV) as a drug is limited due to its poor bioavailability. This study aimed to investigate a series of RSV derivatives (1a-j) with better pharmacokinetic profiles. Among them, derivatives 1d and 1h showed increased cell viability compared to RSV. Further studies demonstrated that both 1d and 1h exhibited positive effects on cell viability, proliferation, and gene expression in various cells involved in oral wound healing. Additionally, 1d and 1h showed promising physicochemical properties and stability, indicating their potential as RSV-based agents for oral tissue repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Biochemistry & Molecular Biology
Antonio Di Stefano
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Alessandro Bonifazi, Fabio Del Bello, Gianfabio Giorgioni, Alessandro Piergentili, Elizabeth Saab, Luca Botticelli, Carlo Cifani, Emanuela Micioni Di Bonaventura, Maria Vittoria Micioni Di Bonaventura, Wilma Quaglia
Summary: Orexin-A and Orexin-B are highly conserved hypothalamic neuropeptides that mediate their effects through two distinct G protein-coupled receptors, OX1-R and OX2-R. They play important roles in various physiological functions such as sleep-wake cycle regulation, emotion, panic-like behaviors, anxiety/stress, food intake, and energy homeostasis. This review focuses on the medicinal chemistry aspects of small molecules acting as dual or subtype selective OX1-R/OX2-R agonists and antagonists, as well as radiolabeled OX-R ligands for molecular imaging.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Oncology
Sara Pagotto, Pasquale Simeone, Davide Brocco, Giulia Catitti, Domenico De Bellis, Simone Vespa, Natalia Di Pietro, Lisa Marinelli, Antonio Di Stefano, Serena Veschi, Laura De Lellis, Fabio Verginelli, Francesco Kaitsas, Manuela Iezzi, Assunta Pandolfi, Rosa Visone, Nicola Tinari, Ignazio Caruana, Mauro Di Ianni, Alessandro Cama, Paola Lanuti, Rosalba Florio
Summary: This review highlights the potential of CAR-T-derived extracellular vesicles (EVs) as therapeutic agents in tumors. CAR-T lymphocytes have shown potential effectiveness in immunotherapy against refractory neoplastic diseases. However, physical barriers, hostile microenvironment, and tumor heterogeneity limit their efficacy against solid tumors. The use of CAR-T-derived EVs as therapeutic agents may enhance CAR-T homing and overcome some adverse effects.
Article
Food Science & Technology
Lucia Recinella, Maria Loreta Libero, Valentina Citi, Annalisa Chiavaroli, Alma Martelli, Roberta Foligni, Cinzia Mannozzi, Alessandra Acquaviva, Simonetta Di Simone, Vincenzo Calderone, Giustino Orlando, Claudio Ferrante, Serena Veschi, Anna Piro, Luigi Menghini, Luigi Brunetti, Sheila Leone
Summary: Multiple studies have shown that aged black garlic has anti-inflammatory, antioxidant, and cardioprotective effects. This study investigated the protective effects of aged black garlic extract (ABGE) alone or in combination with multivitamins on mouse hearts exposed to E. coli lipopolysaccharide. The study also examined the hydrogen sulfide releasing properties and membrane hyperpolarization effect of the formulation composed of ABGE and multivitamins using human aortic smooth muscle cells (HASMCs). The results showed that ABGE, vitamins D and C, and the formulation suppressed the expression of inflammatory genes on mouse hearts and the formulation increased intracellular hydrogen sulfide formation, suggesting its potential use in cardiovascular disease.
Article
Chemistry, Medicinal
Lucia Recinella, Barbara De Filippis, Maria Loreta Libero, Alessandra Ammazzalorso, Annalisa Chiavaroli, Giustino Orlando, Claudio Ferrante, Letizia Giampietro, Serena Veschi, Alessandro Cama, Federica Mannino, Irene Gasparo, Alessandra Bitto, Rosa Amoroso, Luigi Brunetti, Sheila Leone
Summary: The effects of four new PPAR ligands on inflammation and oxidative stress were investigated, and one of them showed potential as a valuable pharmacological tool.
Article
Chemistry, Medicinal
Ivana Cacciatore, Sonia Spalletta, Annalisa Di Rienzo, Vincenzo Flati, Erika Fornasari, Laura Pierdomenico, Piero Del Boccio, Silvia Valentinuzzi, Erica Costantini, Elena Toniato, Stefano Martinotti, Carmela Conte, Antonio Di Stefano, Iole Robuffo
Summary: This study synthesized a series of carvacrol derivatives and found that one derivative, CD3, exhibited anti-obesity and anti-inflammatory effects.
Article
Health Care Sciences & Services
Michele Ciulla, Lisa Marinelli, Giuseppe Di Biase, Ivana Cacciatore, Fiorenzo Santoleri, Alberto Costantini, Marilisa Pia Dimmito, Antonio Di Stefano
Summary: This systematic study analyzes the differences between the European and American healthcare systems in terms of pharmaceutical market approach. It emphasizes the use of managed entry agreements (MEAs) in European countries, as opposed to the unregulated pharmaceutical prices in the American market. Data were collected from various sources, and a literature review was conducted to gather information from the past ten years. The comparison reveals the importance of market access regulation in reducing therapy costs and improving the efficiency, quality, and accessibility for patients.
Article
Pharmacology & Pharmacy
Luca Botticelli, Emanuela Micioni Di Bonaventura, Fabio Del Bello, Gianfabio Giorgioni, Alessandro Piergentili, Wilma Quaglia, Alessandro Bonifazi, Carlo Cifani, Maria Vittoria Micioni Di Bonaventura
Summary: Neuromedin U (NMU) is a bioactive peptide involved in multiple physiological processes, acting through two G protein coupled receptors (GPCR). NMU plays a role in regulating food intake and has anti-obesity properties. It also influences binge eating behavior, suggesting its potential as a therapeutic target for obesity and eating disorders.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Nutrition & Dietetics
Ester Percaccio, Marta De Angelis, Alessandra Acquaviva, Giovanna Nicotra, Claudio Ferrante, Gabriela Mazzanti, Silvia Di Giacomo, Lucia Nencioni, Antonella Di Sotto
Summary: Respiratory viral infections are challenging for susceptible and immunocompromised individuals. The study developed a mixture of Echinacea purpurea and Humulus lupulus extracts with antioxidant, cytoprotective, immunomodulating, and antiviral activities. Nrf2 activation may play a role in these properties. Further research can increase interest in this product.
Article
Microbiology
Paola Angelini, Giancarlo Angeles Flores, Gaia Cusumano, Roberto Venanzoni, Roberto Maria Pellegrino, Gokhan Zengin, Simonetta Cristina Di Simone, Luigi Menghini, Claudio Ferrante
Summary: This research investigated the impact of different substrates on the metabolite compositions of Hypsizygus marmoreus mycelia, and found that extracts from substrates enriched with barley malt or grape pomace demonstrated high antibacterial activity against various strains. Extracts from mushroom cultivated in grape pomace-enriched substrate also showed remarkable efficacy against Trichophyton mentagrophytes and T. tonsurans. This study contributes to the understanding of the cultivation of H. marmoreus.
Article
Biochemistry & Molecular Biology
Kassim Bakar, Nilofar, Andilyat Mohamed, Lukasz Swiatek, Benita Hryc, Elwira Sieniawska, Barbara Rajtar, Claudio Ferrante, Luigi Menghini, Gokhan Zengin, Malgorzata Polz-Dacewicz
Summary: This study conducted comprehensive chemical profiling and biological tests of Vepris boiviniana extracts from different parts. The results indicate that the extracts have potential antioxidant, enzyme inhibitory, and cytotoxicity activities, making them promising for cancer treatment.
Article
Cell Biology
Lucia Recinella, Maria Loreta Libero, Serena Veschi, Anna Piro, Guya Diletta Marconi, Francesca Diomede, Annalisa Chiavaroli, Giustino Orlando, Claudio Ferrante, Rosalba Florio, Alessia Lamolinara, Renzhi Cai, Wei Sha, Andrew V. Schally, Roberto Salvatori, Luigi Brunetti, Sheila Leone, Markus Fendt
Summary: This study investigated the effects of a GHRH antagonist, MIA-602, on emotional disorders and explored the underlying mechanisms. The results showed that MIA-602 treatment and GHRH gene deficiency were associated with anxiolytic and antidepressant behavior. Additionally, the study found that MIA-602 treatment activated Nrf2, HO1, and NQO1, while downregulating COX-2, iNOS, NFkB, and TNF-alpha expressions. These findings suggest a dysregulation of neural pathways caused by GHRH gene deficiency, which is mimicked by GHRH antagonist treatment.
