Increasing cGMP is a unique therapeutic principle, and drugs inhibiting cGMP-degrading enzymes or stimulating cGMP production are approved for the treatment of various diseases such as erectile dysfunction, coronary artery disease, pulmonary hypertension, chronic heart failure, irritable bowel syndrome, or achondroplasia. In addition, cGMP-increasing therapies are preclinically profiled or in clinical development for quite a broad set of additional indications, e.g., neurodegenerative diseases or different forms of dementias, bone formation disorders, underlining the pivotal role of cGMP signaling pathways. The fundamental understanding of the signaling mediated by nitric oxide-sensitive (soluble) guanylyl cyclase and membrane-associated receptor (particulate) guanylyl cyclase at the molecular and cellular levels, as well as in vivo, especially in disease models, is a key prerequisite to fully exploit treatment opportunities and potential risks that could be associated with an excessive increase in cGMP. Furthermore, human genetic data and the clinical effects of cGMP-increasing drugs allow back-translation into basic research to further learn about signaling and treatment opportunities. The biannual international cGMP conference, launched nearly 20 years ago, brings all these aspects together as an established and important forum for all topics from basic science to clinical research and pivotal clinical trials. This review summarizes the contributions to the "10th cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications," which was held in Augsburg in 2022 but will also provide an overview of recent key achievements and activities in the field of cGMP research.
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http://dx.doi.org/10.1007/s00210-023-02484-8 | DOI Listing |
Appl Microbiol Biotechnol
January 2025
Grup d'Enginyeria de Bioprocessos i Biocatàlisi Aplicada, ENG4BIO, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, Cerdanyola del Vallès, 08193, Barcelona, Spain.
Several strategies have been developed in recent years to improve virus-like particle (VLP)-based vaccine production processes. Among these, the metabolic engineering of cell lines has been one of the most promising approaches. Based on previous work and a proteomic analysis of HEK293 cells producing Human Immunodeficiency Virus-1 (HIV-1) Gag VLPs under transient transfection, four proteins susceptible of enhancing VLP production were identified: ataxia telangiectasia mutated (ATM), ataxia telangiectasia and rad3-related (ATR), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta (PDEδ).
View Article and Find Full Text PDFLife Sci
December 2024
Department of Rehabilitation Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; The First Clinical Medical College School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Provincial Key Laboratory of Trauma, Burn and Pain Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address:
Aims: This study explores the potential of neuromodulation, specifically transcranial alternating current stimulation (tACS), as a promising rehabilitative therapy in spinal cord injury (SCI).
Main Methods: By meticulously optimizing treatment parameters and durations, our objective was to enhance nerve regeneration and facilitate functional recovery. To assess the efficacy of tACS, our experiments used the rat T10 SCI model.
Proc Natl Acad Sci U S A
January 2025
Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52242.
Cone cGMP-phosphodiesterase (PDE6) is the key effector enzyme for daylight vision, and its properties are critical for shaping distinct physiology of cone photoreceptors. We determined the structures of human cone PDE6C in various liganded states by single-particle cryo-EM that reveal essential functional dynamics and adaptations of the enzyme. Our analysis exposed the dynamic nature of PDE6C association with its regulatory γ-subunit (Pγ) which allows openings of the catalytic pocket in the absence of phototransduction signaling, thereby controlling photoreceptor noise and sensitivity.
View Article and Find Full Text PDFMol Biol Rep
December 2024
Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran.
This study conducts an in-depth review of the correlation between testis tissue changes and circulating microRNAs (miRNA) in diabetes-induced male reproductive complications, drawing upon both animal and clinical studies. The original articles published in English that specifically investigate miRNAs linked to male infertility in humans or animals with either type I or ΙΙ diabetes mellitus were included. The relevant articles were gathered from the PubMed, Google Scholar, Cochrane Library, and ScienceDirect databases.
View Article and Find Full Text PDFBiol Proced Online
December 2024
Department of Radiation Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, China.
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