Article
Neurosciences
Josep Tomas, Maria A. Lanuza, Manel M. Santafe, Victor Cilleros-Mane, Laia Just-Borras, Marta Balanya-Segura, Aleksandra Polishchuk, Laura Nadal, Marta Tomas, Neus Garcia
Summary: In recent years, the role of muscarinic acetylcholine receptors (mAChRs) in the mammalian neuromuscular junction (NMJ) has been extensively studied. The presence of mAChRs in the presynaptic membrane allows for autocrine feedback and direct activity-dependent interaction between competing axons during development. They also interact with other metabotropic receptors, downstream kinases, and voltage-gated calcium channels (VGCCs) to regulate synaptic elimination and monoinnervation of musculoskeletal cells.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Malka Cohen-Armon
Summary: Previous studies suggested that the affinity of seven-transmembrane muscarinic acetylcholine receptors for agonists is influenced by membrane depolarization, but recent reports propose a voltage sensor in the muscarinic receptor. However, experiments measuring acetylcholine binding to muscarinic receptors in brain synaptoneurosomes contradict this explanation. These findings indicate that the voltage-dependent sodium channel (VDSC) acts as the voltage sensor, causing Go-protein activation in response to membrane depolarization, which then modulates the affinity of muscarinic receptors for cholinergic agonists.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
David M. M. Shostak, Stephanie Constantin, Jill Flannery, Susan Wray
Summary: Gonadotropin-releasing hormone (GnRH)-secreting neurons, controlled by acetylcholine (ACh), directly regulate fertility by modulating gonadotrophs in the anterior pituitary. Calcium imaging experiments reveal that ACh can directly modulate GnRH neuronal activity. Cholinergic cells in septal areas are the source of ACh afferents contacting GnRH neurons.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Food Science & Technology
Andrea Pathe-Neuschaefer-Rube, Frank Neuschaefer-Rube, Gerhard P. Pueschel
Summary: The newly developed cell-based functional assay showed specificity in detecting the activity of neurotoxins and neuroactive pharmaceuticals that affect calcium-dependent neurotransmitter release. The assay can be a versatile tool for analyzing the biological efficiency of these compounds.
Article
Chemistry, Medicinal
Marlon Millard, Jonas Kilian, Marius Ozenil, Mariella Mogeritsch, Verena Schwingenschloegl-Maisetschlaeger, Wolfgang Holzer, Marcus Hacker, Thierry Langer, Verena Pichler
Summary: Our research group has identified a new compound as a starting point for designing muscarinic acetylcholine receptor ligands. We have developed promising compounds with favorable drug-like attributes and potential CNS activity. These compounds have the potential for radiolabeling applications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Qian Zhang, Ying Jia, Pan Pan, Xiuping Zhang, Yanfei Jia, Ping Zhu, Xiaowei Chen, Yang Jiao, Guiyu Kang, Lulu Zhang, Xiaoli Ma
Summary: This study uncovers a new interaction between alpha 5-nAChR and Ly6E that inhibits cancer cell migration by modulating the TGF-beta 1/Smad signaling pathway in NSCLC.
Editorial Material
Multidisciplinary Sciences
Declan Manning, L. Fernando Santana
Summary: The authors of this study present an approach using functionalized nanobodies to reduce the activity of voltage-gated Ca2+ channels associated with beta(1) subunits and facilitate their removal from the surface membrane of neurons and muscle.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Kelly Smart, Mika Naganawa, Stephen R. Baldassarri, Nabeel Nabulsi, Jim Ropchan, Soheila Najafzadeh, Hong Gao, Antonio Navarro, Vanessa Barth, Irina Esterlis, Kelly P. Cosgrove, Yiyun Huang, Richard E. Carson, Ansel T. Hillmer
Summary: The study aimed to explore the variation of acetylcholine (Ach) across the human brain using positron emission tomography (PET) imaging estimates of drug occupancy at cholinergic receptors. Results showed consistently lower occupancy estimates within striatal regions, indicating higher ACh concentration, and provided the first in vivo estimates of regional variation in ACh concentration in the living brain.
Article
Biochemistry & Molecular Biology
Jonas Kilian, Marlon Millard, Marius Ozenil, Dominik Krause, Khadija Ghaderi, Wolfgang Holzer, Ernst Urban, Helmut Spreitzer, Wolfgang Wadsak, Marcus Hacker, Thierry Langer, Verena Pichler
Summary: The muscarinic acetylcholine receptor family is a highly sought-after target for neurological disorders. Despite previous failures to develop subtype-selective ligands, this study successfully synthesized a series of arecaidine-derived ligands with potential blood-brain barrier permeability and determined their binding affinities towards each of the individual human mAChR subtypes. The most promising compound of this series showed high selectivity towards hM(1) and acted as an antagonist. Overall, this study expands our understanding of the structure-activity relationship and provides guidance for the development of highly selective mAChR ligands.
Article
Biochemistry & Molecular Biology
Ji-Eun Kim, Yun-Ju Choi, Su-Jin Lee, Jeong-Eun Gong, You-Jung Jin, So-Hae Park, Hee-Seob Lee, Young-Whan Choi, Jin-Tae Hong, Dae-Youn Hwang
Summary: This study demonstrated that exposure to Pt improves the constipation phenotype in SD rats with Lop-induced constipation by regulating membrane water channel expression, GI hormones, the mAChR signaling pathway, and fecal microbiota.
Review
Biochemistry & Molecular Biology
Roberta Piovesana, Adam J. Reid, Ada Maria Tata
Summary: The communication between neurons and glial cells has been well-documented in various stages of development and disease. Neurotransmitters, especially acetylcholine, play a significant role in regulating the development and physiology of glial cells. This review focuses on the contribution of neurotransmitter receptors, particularly the M2 muscarinic receptor and the alpha 7 nicotinic receptor, in influencing the phenotype and functioning of Schwann cells. Understanding these interactions can help identify potential therapeutic targets for pathological conditions involving glial cells.
Review
Biochemistry & Molecular Biology
Dorina Zoephel, Chantal Hof, Annette Lis
Summary: Aging is an unstoppable process that affects every cell of the organism, especially the changes in Ca2+ signaling in immune cells which may profoundly impact the development of age-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Osman Ali, Mazen Tolaymat, Shien Hu, Guofeng Xie, Jean-Pierre Raufman
Summary: Despite the challenges in treating colorectal cancer, targeting muscarinic receptors and MMPs shows promise in inhibiting tumor growth and progression. Selective approaches can help overcome potential off-target effects, allowing clinicians to exploit these pathways for therapeutic purposes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nathalia M. Pinheiro, Rosana Banzato, Iolanda Tiberio, Marco A. M. Prado, Vania F. Prado, Ayman K. Hamouda, Carla M. Prado
Summary: In acute lung injury, inflammatory markers are significantly elevated in cholinergic-deficient mice compared to wild-type, but treatment with the selective alpha 7 nicotinic receptor agonist PNU 282987 can restore the response and reduce lung inflammation. The anti-inflammatory effects of the lung cholinergic system are associated with an increase in the level of alpha 7 nicotinic receptors, suggesting potential clinical applications for treating acute lung injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Enes Akyuz, Zueleyha Doganyigit, Asli Okan, Seher Yilmaz, Sumeyye Ucar, Ali Tugrul Akin
Summary: This study aimed to observe the immunoreactivity of muscarinic ACh receptor and potassium channel in the cuprizone model, which may play a significant role in diseases like Multiple Sclerosis. The results showed that demyelination in the female animals could lead to changes in muscarinic ACh receptor and potassium channel in the brainstem, vagus nerve, and heart. These findings have important implications for the research and treatment of related diseases.
BRAIN RESEARCH BULLETIN
(2023)