Orphan GPCRs in Neurodegenerative Disorders: Integrating Structural Biology and Drug Discovery Approaches DOI Creative Commons
June‐Ki Kim,

Chulwon Choi

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(10), С. 11646 - 11664

Опубликована: Окт. 19, 2024

Neurodegenerative disorders, particularly Alzheimer's and Parkinson's diseases, continue to challenge modern medicine despite therapeutic advances. Orphan G-protein-coupled receptors (GPCRs) have emerged as promising targets in the central nervous system, offering new avenues for drug development. This review focuses on structural biology of orphan GPCRs implicated these providing a comprehensive analysis their molecular architecture functional mechanisms. We examine recent breakthroughs determination techniques, such cryo-electron microscopy X-ray crystallography, which elucidated intricate conformations receptors. The highlights how insights inform our understanding GPCR activation, ligand binding signaling pathways. By integrating data with pharmacology, we explore potential structure-guided approaches developing targeted therapeutics toward GPCRs. structural-biology-centered perspective aims deepen comprehension guide future discovery efforts neurodegenerative disorders.

Язык: Английский

Impact of cannabinoids on cancer outcomes in patients receiving immune checkpoint inhibitor immunotherapy DOI Creative Commons

MariaLuisa Vigano,

Lixing Wang,

Alia As’sadiq

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 5, 2025

Cannabinoids relieve pain, nausea, anorexia and anxiety, improve quality of life in several cancer patients. The immunotherapy with checkpoint inhibitors (ICIs), although very successful a subset patients, is accompanied by moderate to severe immune-related adverse events (ir-AE) that often necessitate its discontinuation. Because their role symptomatic relief, cannabinoids have been used combination immune inhibitor (ICI) immunotherapy. A few studies strongly suggest the use medicinal cannabis patients attenuates many ir-AE associated ICI increase tolerability. However, no significant beneficial effects on overall survival, progression free survival or relapses were observed; rather, some noted concurrent administration clinical benefits latter. cannabinoids' well documented immunosuppressive mediated through cannabinoid recptor-2 (CB2), we propose considering this receptor as an inhibitory per se. simultaneous neutralization CB2, treatment, may lead better outcomes receiving In regard, such cannabidiol (CBD) cannabigerol (CBG), little agonism for be therapeutic choices. Additional strategies e.g., monoacylglycerol lipase (MAGL) degrade endocannabinoids lipogenesis formation lipid bilayers cells also explored. Future should take into consideration gut microbiota, CYP450 polymorphism haplotypes, cannabinoid-drug interactions genetic somatic variations occurring receptors signaling pathways personalized cannabis-based therapies ICIs. This rational knowledge-based regimens tailored individual

Язык: Английский

Процитировано

1

Modulation of neuroinflammation and oxidative stress by targeting GPR55 – new approaches in the treatment of psychiatric disorders DOI Creative Commons

Matthias Apweiler,

Soraya Wilke Saliba, Lu Sun

и другие.

Molecular Psychiatry, Год журнала: 2024, Номер 29(12), С. 3779 - 3788

Опубликована: Май 25, 2024

Pharmacological treatment of psychiatric disorders remains challenging in clinical, pharmacological, and scientific practice. Even if many different substances are established for treating conditions, subgroups patients show only small or no response to the treatment. The neuroinflammatory hypothesis genesis might explain underlying mechanisms these non-responders. For that reason, recent research focus on processes oxidative stress as possible causes disorders. G-protein coupled receptors (GPCRs) form biggest superfamily membrane-bound already well known pharmacological targets various diseases. receptor 55 (GPR55), a considered part endocannabinoid system, reveals promising modulation processes. Different agonists antagonists reduce pro-inflammatory cytokine release, enhance synthesis anti-inflammatory mediators, protect cells from damage. this GPR55 ligands be compounds suffering related neuroinflammation stress. New approaches drug design lead new targeting pathomechanisms those just one molecule.

Язык: Английский

Процитировано

4

The role of cannabinoid-mediated signaling pathways and mechanisms in brain disorders DOI
Shunfeng Liu, Zegang Ma

Cellular Signalling, Год журнала: 2025, Номер unknown, С. 111653 - 111653

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0

The endocannabinoid and paracannabinoid systems in natural reward processes: possible pharmacological targets? DOI Creative Commons
Marzia Friuli, Barbara Eramo,

C. Sepe

и другие.

Physiology & Behavior, Год журнала: 2025, Номер 296, С. 114929 - 114929

Опубликована: Апрель 22, 2025

Язык: Английский

Процитировано

0

Cannabis, Endocannabinoids and Brain Development: From Embryogenesis to Adolescence DOI Creative Commons
Ricardo J. Rodrigues, Joana M. Marques, Attila Köfalvi

и другие.

Cells, Год журнала: 2024, Номер 13(22), С. 1875 - 1875

Опубликована: Ноя. 13, 2024

The endocannabinoid signalling system (ECS) plays a critical role from the very beginning of embryogenesis. Accordingly, ECS is engaged early on in nervous development, starting neurulation, supported by identification components—both receptors and enzymes controlling metabolism—at these stages. In particular, regarding brain, involved tightly regulated sequence events that comprise brain neurogenesis to neuronal migration, morphological guidance for connectivity, synaptic circuitry refinement. importance this broad across various development processes further underscored growing understanding consequences cannabis exposure at different developmental Despite considerable knowledge we have significant gaps our remain, particularly long-term impact underlying mechanisms This review provides an overview current state throughout embryogenesis adulthood, discusses exposure, especially during adolescence—a period maturation refinement coinciding with increased risk use.

Язык: Английский

Процитировано

3

Orphan GPCRs in Neurodegenerative Disorders: Integrating Structural Biology and Drug Discovery Approaches DOI Creative Commons
June‐Ki Kim,

Chulwon Choi

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(10), С. 11646 - 11664

Опубликована: Окт. 19, 2024

Neurodegenerative disorders, particularly Alzheimer's and Parkinson's diseases, continue to challenge modern medicine despite therapeutic advances. Orphan G-protein-coupled receptors (GPCRs) have emerged as promising targets in the central nervous system, offering new avenues for drug development. This review focuses on structural biology of orphan GPCRs implicated these providing a comprehensive analysis their molecular architecture functional mechanisms. We examine recent breakthroughs determination techniques, such cryo-electron microscopy X-ray crystallography, which elucidated intricate conformations receptors. The highlights how insights inform our understanding GPCR activation, ligand binding signaling pathways. By integrating data with pharmacology, we explore potential structure-guided approaches developing targeted therapeutics toward GPCRs. structural-biology-centered perspective aims deepen comprehension guide future discovery efforts neurodegenerative disorders.

Язык: Английский

Процитировано

0