Article
Behavioral Sciences
Batoul Mirbolouk, Kambiz Rohampour, Mohammad Rostampour, Adele Jafari, Behrooz Khakpour-Taleghani
Summary: This study evaluated the role of Orx1R in depressive behaviors using the CMS model, showing that chronic Orx1R antagonism alleviates depressive behaviors induced by CMS and improves PSD-95 expression in PFC.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Konstantina Vraka, Dimitrios Mytilinaios, Andreas P. Katsenos, Anastasios Serbis, Stavros Baloyiannis, Stefanos Bellos, Yannis V. Simos, Nikolaos P. Tzavellas, Spyridon Konitsiotis, Patra Vezyraki, Dimitrios Peschos, Konstantinos I. Tsamis
Summary: This study provides information about the distribution of OX1R in the human hypothalamus. OX1R is mainly found in the lateral hypothalamic area, the lateral preoptic nucleus, the supraoptic nucleus, the dorsomedial nucleus, the ventromedial nucleus, and the paraventricular nucleus. The majority of neurons in these areas (over 80%) express OX1R, with particularly high expression in the lateral tuberal nucleus (over 95% of neurons). These results reveal the distribution of OX1R at the cellular level and discuss its regulatory role in the hypothalamus.
Article
Neurosciences
Dan Han, Yuxiu Shi, Fang Han
Summary: The orexin system plays a role in anxiety- and depression-related symptoms observed in PTSD. Single prolonged stress (SPS) induces enhanced anxiety levels, reduced exploratory activities, and anhedonia in rats, with intracerebroventricular administration of orexin-A alleviating these behavioral changes.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Review
Neurosciences
Natasha C. Dale, Daniel Hoyer, Laura H. Jacobson, Kevin D. G. Pfleger, Elizabeth K. M. Johnstone
Summary: The orexin system consists of two G protein-coupled receptors, OX1 and OX2 receptors, along with two endogenous agonists. Orexin receptor coupling is diverse and can vary depending on tissue, cell, and context. Ligands, receptor-protein interactions, and cellular environment play important roles in the G protein coupling profiles of the orexin receptors. This has implications for understanding the function of the orexin system and developing drugs targeting it.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Yoshiaki Ohi, Yuki Asai, Daisuke Kodama
Summary: Orexins, produced in the hypothalamus and distributed in the central nervous system, regulate various physiological functions. Activation of orexin-1 receptor (OX1R) in the nucleus tractus solitarius has dual effects on excitatory synaptic transmission, increasing spontaneous transmission frequency and inhibiting evoked transmission, mediated by stimulating NO production and releasing endocannabinoids respectively.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Anatomy & Morphology
Erzsebet Farkas, Anett Szilvasy-Szabo, Yvette Ruska, Richard Sinko, Morten Gronbech Rasch, Thomas Egebjerg, Charles Pyke, Balazs Gereben, Lotte Bjerre Knudsen, Csaba Fekete
Summary: GLP-1R protein is mainly distributed in circumventricular organs and neighboring regions such as the arcuate nucleus and nucleus tractus solitarii in the rat brain. Additionally, GLP-1R protein is also present in various areas of the telencephalon, diencephalon, brainstem, and cerebellum. Ultrastructural examination reveals that GLP-1R immunoreactivity is associated with the membrane of perikarya and dendrites, and can also be found inside and on the surface of axon varicosities and terminals.
BRAIN STRUCTURE & FUNCTION
(2021)
Article
Neurosciences
Dexin Zhang, Ying Cui, Manman Zhao, Xuecheng Zheng, Chunyan Li, Jingbo Wei, Kaijie Wang, Jianzhong Cui
Summary: This study demonstrates that OXA suppresses autophagy via the OXR1-mediated ERK/mTOR signaling pathway to exert neuroprotective effects, and it might provide a novel therapeutic approach in patients suffering from ICH.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Clinical Neurology
Maria P. Mogavero, Alessandro Silvani, Giuseppe Lanza, Lourdes M. DelRosso, Luigi Ferini-Strambi, Raffaele Ferri
Summary: After describing orexins and their roles in sleep and medical disorders, the article discusses the clinical evidence on the effects of DORAs and SORAs on insomnia to provide recommendations for further assessment in personalized and precision medicine. Trials with orexin receptor antagonists have shown potential as a valid therapeutic option for insomnia in various medical conditions, but more studies are needed to determine the most suitable options for different patient populations.
NATURE AND SCIENCE OF SLEEP
(2023)
Article
Pharmacology & Pharmacy
Francisco Mateus Gonsalves Trajano, Luana Talinne da Costa Gomes, Pedro Brutch Dantas, Maele Oliveira de Sena, Jonas Ivan Nobre Oliveira, Sabatino Ventura, Elaine Cristina Gavioli, Edilson Dantas da Silva Jr
Summary: This study found that histamine can induce phasic contractions of the rat distal cauda epididymis duct via H2 receptors and autonomic neurotransmitters. It may also have modulatory actions on contractions induced by adrenergic receptor agonists. Further research is needed to determine the localization of histamine receptors in the epididymal duct and the effects of manipulating the histaminergic system on epididymal function and male fertility.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Anthony Markham
Summary: Daridorexant, an orally administered dual orexin receptor antagonist, has been approved in the USA for the treatment of insomnia based on the results of pivotal phase III trials.
Article
Multidisciplinary Sciences
Rebecca Evans, Haruhide Kimura, Robert Alexander, Ceri H. Davies, Helene Faessel, Deborah S. Hartman, Takashi Ishikawa, Emiliangelo Ratti, Kohei Shimizu, Motohisa Suzuki, Shinichiro Tanaka, Hiroshi Yukitake, Yves Dauvilliers, Emmanuel Mignot
Summary: Narcolepsy is a sleep disorder that can be classified into type 1 and type 2. The drug danavorexton shows promising results in treating narcolepsy by targeting both orexin 1 and orexin 2 receptors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Andrew S. Huhn, Patrick H. Finan, Charlene E. Gamaldo, Alexis S. Hammond, Annie Umbricht, Cecilia L. Bergeria, Eric C. Strain, Kelly E. Dunn
Summary: This study examined the use of a dual-orexin receptor antagonist in opioid withdrawal and found that it may have potential benefits for improving sleep and withdrawal outcomes.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Pilar Marcos, Rafael Covenas
Summary: Understanding the dysregulation of hypothalamic neuropeptides is crucial in studying feeding behavior and obesity. Current pharmacological strategies for obesity treatment are ineffective, highlighting the need for new therapeutic approaches. This review focuses on the involvement of the orexinergic system in feeding behavior, discussing animal models, human studies, and the connection to other substances. Promising research on orexinergic signaling pathways, heterogeneity of hypothalamic orexinergic neurons, receptor-receptor interaction, and sex differences are highlighted. The development of combination therapies and more specific orexin receptor antagonists is important for successful anti-obesity treatments.
APPLIED SCIENCES-BASEL
(2022)
Article
Behavioral Sciences
Archana Durairaja, Ceylan-Scarlett Steinecke, Markus Fendt
Summary: The study found that orexin 1 receptor antagonist impairs cognitive flexibility in a sex-dependent manner, affecting females more than males. Consumption of the reward used in the ASST was not affected by the antagonist, indicating a specific impact on cognitive flexibility rather than reward response.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Endocrinology & Metabolism
Hongming Ye, Tong Cao, Qigang Shu, Yue Chen, Yongli Lu, Zhi He, Zicheng Li
Summary: The orexin receptor 1 (OX1R) plays a crucial role in mediating anxiety during drug withdrawal in opioid addicts. Inhibition of OX1R alleviates anxiety-like behaviors in abstinent mice, and the expression of OX1R is upregulated during morphine withdrawal.
PSYCHONEUROENDOCRINOLOGY
(2023)
Review
Chemistry, Applied
Simona Tafuri, Natascia Cocchia, Anastasia Vassetti, Domenico Carotenuto, Luigi Esposito, Lucianna Maruccio, Luigi Avallone, Francesca Ciani
Summary: Maca is an edible root plant grown in the Andean region of Peru, known for its nutritional and therapeutic properties. It is rich in nutritional elements and secondary metabolites with high biological activity. Studies have shown various biological effects of Maca on male reproduction.
NATURAL PRODUCT RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Valeria De Pasquale, Michele Costanzo, Rosa Anna Siciliano, Maria Fiorella Mazzeo, Valeria Pistorio, Laura Bianchi, Emanuela Marchese, Margherita Ruoppolo, Luigi Michele Pavone, Marianna Caterino
Article
Biochemistry & Molecular Biology
Valeria De Pasquale, Marianna Caterino, Michele Costanzo, Roberta Fedele, Margherita Ruoppolo, Luigi Michele Pavone
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Biochemistry & Molecular Biology
Valeria De Pasquale, Luigi Michele Pavone
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Agriculture, Dairy & Animal Science
Danila D'Angelo, Francesca Ciani, Alessandra Zaccherini, Simona Tafuri, Luigi Avallone, Serenella d'Ingeo, Angelo Quaranta
Review
Biochemistry & Molecular Biology
Valeria De Pasquale, Miriam Shasa Quiccione, Simona Tafuri, Luigi Avallone, Luigi Michele Pavone
Summary: Heparan sulfate proteoglycans (HSPGs) are a group of glycoproteins with diverse structures, capable of interacting with various ligands to regulate cellular processes; they also assist many viruses in invading host cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Gianluca Scerra, Valeria De Pasquale, Luigi Michele Pavone, Maria Gabriella Caporaso, Andreas Mayer, Maurizio Renna, Massimo D'Agostino
Summary: This study demonstrates how the acute accumulation of a single substrate leads to rapid redistribution of lysosomes, causing their expansion and reducing secretion by inhibiting organelle motility towards the plasma membrane. Furthermore, evidence suggests that these defects may be due to extensive contacts between enlarged lysosomes and the intertwined membrane structures of the endoplasmic reticulum, potentially leading to secondary defects observed in LSD models and patients.
Article
Biochemistry & Molecular Biology
Valeria De Pasquale, Gianluca Scerra, Melania Scarcella, Massimo D'Agostino, Luigi Michele Pavone
Summary: Mucopolysaccharidoses (MPSs) are a group of inherited lysosomal storage disorders caused by deficiency of lysosomal enzymes, leading to glycosaminoglycan accumulation and tissue dysfunction. Current treatments for MPS III do not cure the disease, but NK1 treatment shows potential in improving neurological symptoms by reducing lysosomal pathology and promoting neuronal differentiation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Editorial Material
Biochemistry & Molecular Biology
Valeria De Pasquale, Melania Scarcella, Luigi Michele Pavone
Review
Biochemistry & Molecular Biology
Melania Scarcella, Danila d'Angelo, Mariangela Ciampa, Simona Tafuri, Luigi Avallone, Luigi Michele Pavone, Valeria De Pasquale
Summary: Cathepsins are a family of proteases involved in protein degradation and turnover. Their dysregulation has been associated with various human diseases. In viral infections, cathepsins play crucial roles and their inhibitors have potential therapeutic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Agriculture, Dairy & Animal Science
Chiara Del Prete, Alfonso Calabria, Valentina Longobardi, Veronica Palumbo, Barbara Merlo, Eleonora Iacono, Simona Tafuri, Domenico Carotenuto, Francesca Ciani, Sara Damiano, Roberto Ciarcia, Natascia Cocchia
Summary: The addition of Maca extract to canine chilled extender showed positive effects on sperm hyperactivation and DNA integrity in short-term storage. However, high concentrations of Maca had immediately deleterious effects on semen quality. Maca supplementation also increased sperm hyperactivation, preserved DNA integrity, and reduced lipid peroxidation in short-term storage.
Article
Chemistry, Medicinal
Valeria De Pasquale, Anna Esposito, Gianluca Scerra, Melania Scarcella, Mariangela Ciampa, Antonietta Luongo, Daniele D'Alonzo, Annalisa Guaragna, Massimo D'Agostino, Luigi Michele Pavone
Summary: Sanfilippo syndrome is a group of genetic diseases characterized by the accumulation of heparan sulfate (HS) in lysosomes and other cellular compartments, leading to tissue and organ dysfunctions. This study found that N-substituted L-iminosugars can reduce substrate storage and lysosomal dysfunctions in Sanfilippo fibroblasts and a neuronal cellular model of Sanfilippo B subtype. These compounds also increase the levels of defective enzyme alpha-N-acetylglucosaminidase and correct its sorting, as well as reduce HS accumulation by downregulating protein levels of exostosin glycosyltransferases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Valeria De Pasquale, Anna Esposito, Gianluca Scerra, Melania Scarcella, Mariangela Ciampa, Antonietta Luongo, Daniele D'Alonzo, Annalisa Guaragna, Massimo D'Agostino, Luigi Michele Pavone
Summary: Sanfilippo syndrome is a group of genetic diseases caused by a lack or decreased activity of enzymes involved in heparan sulfate catabolism. This leads to the accumulation of heparan sulfate in cells, resulting in tissue and organ dysfunctions, including severe neurodegeneration. In this study, N-substituted L-iminosugars were found to significantly reduce substrate storage and lysosomal dysfunctions in Sanfilippo fibroblasts and a neuronal cellular model of Sanfilippo B subtype. They also corrected the sorting of defective alpha-N-acetylglucosaminidase and reduced heparan sulfate accumulation by downregulating exostosin glycosyltransferases. These findings suggest a promising pharmacological potential for these glycomimetics in treating Sanfilippo syndrome.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
