Natural and Synthetic Phosphodiesterase Inhibitors in 2023: an Update on the Impact on Neurological and Psychiatric Conditions DOI
Giovanni Ribaudo, Alessandra Gianoncelli

Mini-Reviews in Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 24(6), P. 568 - 570

Published: Oct. 9, 2023

Abstract: This Perspective provides an updated overview on the involvement of phosphodiesterase (PDE) isoforms and corresponding inhibitors in neurological disorders, including dementia, Parkinson’s disease, multiple sclerosis, neuropsychiatric conditions cerebral ischemia. Particular attention has been dedicated to natural semi-synthetic compounds. Translation into clinic preclinical results, toxicity profile bioavailability represent challenging aspects development PDE inhibitors. With aim providing latest updates reader, 2023 contributions field were considered for preparation this Perspective.

Language: Английский

cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment DOI Creative Commons
Hongying Zhang, Yongliang Liu,

Jieya Liu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Jan. 17, 2024

Cancer is a complex disease resulting from abnormal cell growth that induced by number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells angiogenesis, plays critical role in progression. Cyclic adenosine monophosphate (cAMP) second messenger has pleiotropic effects on the TME. downstream effectors cAMP include cAMP-dependent protein kinase (PKA), exchange activated (EPAC) ion channels. While can activate PKA or EPAC promote cancer growth, it also inhibit proliferation survival context- type-dependent manner. Tumor-associated stromal cells, such as CAF release cytokines factors either stimulate production within Recent studies have shown targeting signaling TME therapeutic benefits cancer. Small-molecule agents adenylate cyclase been to growth. In addition, cAMP-elevating agents, forskolin, not only induce death, but directly some types. this review, we summarize current understanding biology immunology discuss basis for its context-dependent dual oncogenesis. Understanding precise mechanisms interact will be development effective therapies. Future aimed at investigating cAMP-cancer axis regulation may provide new insights into underlying tumorigenesis lead novel strategies.

Language: Английский

Citations

33
cAMP-PKA signaling pathway and anxiety: Where do we go next? DOI

Daokang Chen,

Jingji Wang,

Jian Cao

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 122, P. 111311 - 111311

Published: July 24, 2024

Language: Английский

Citations

6
Negative Symptoms in Schizophrenia: An Update on Research Assessment and the Current and Upcoming Treatment Landscape DOI

Preetika Govil,

Joshua T. Kantrowitz

CNS Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Language: Английский

Citations

0
Modulation of Cognitive Activity by Plant-Based Extracts (Allium cepa, Coffea robusta, and Brassica oleracea) through the Phosphodiesterase 4B inhibition: Insite from a Mice Model Study DOI Creative Commons
Nazir Ahmad, Kaisun Nesa Lesa, Nanang Fakhrudin

et al.

Phytomedicine Plus, Journal Year: 2025, Volume and Issue: unknown, P. 100778 - 100778

Published: March 1, 2025

Language: Английский

Citations

0
PDE7 as a Precision Target: Bridging Disease Modulation and Potential PET Imaging for Translational Medicine DOI Creative Commons

Tao-Qian Zhao,

Steven H. Liang

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Language: Английский

Citations

0
PHOSPHODIESTERASE INHIBITORS FOR TREATMENT OF ALZHEIMER'S DISEASE DOI
Phool Chandra, Vikas Sharma

INDIAN DRUGS, Journal Year: 2024, Volume and Issue: 61(07), P. 7 - 22

Published: July 28, 2024

Cognitive decline with aging is a concern, particularly in neurodegenerative and mental diseases. enhancers focus on cholinergic monoaminergic systems, but Phosphodiesterases (PDEs) have gained interest enhancing cognition by increasing intracellular accessibility of additional messengers. The present study sought to elucidate the effects PDE-Inhibitors perception, feasible underlying mechanisms, their application existing hypotheses regarding formation memories. review examines literature from 2010-2023 various PDE medications processes, including studies PDE-Is relation blood flow, euphoria, long-term potentiation. inhibitors enhance brain information processing, concentration, memory, executive function memory use, likely due an LTP-interrelated mode action. PDE2-Is PDE9-Is are potential candidates for cognitive enhancement, isoform-specific minimal negative properties needed realize fully.

Language: Английский

Citations

3
Bile acid signalling and its role in anxiety disorders DOI Creative Commons

Simin Chen,

Qi Shao,

Jiayi Chen

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 23, 2023

Anxiety disorder is a prevalent neuropsychiatric that afflicts 7.3%~28.0% of the world's population. Bile acids are synthesized by hepatocytes and modulate metabolism via farnesoid X receptor (FXR), G protein-coupled (TGR5), etc. These effects not limited to gastrointestinal tract but also extend tissues organs such as brain, where they regulate emotional centers nerves. A rise in serum bile acid levels can promote interaction between central FXR TGR5 across blood-brain barrier or activate intestinal release fibroblast growth factor 19 (FGF19) glucagon-like peptide-1 (GLP-1), respectively, which turn, transmit signals brain these indirect pathways. This review aimed summarize advancements physiological functions their receptors various tissues, with specific focus on regulatory roles function. The contribution anxiety sending direct pathways was discussed. Different ligands trigger distinct signaling cascades, producing diverse downstream effects, may be involved regulation. Future investigations from perspective anticipated lead novel mechanistic insights potential therapeutic targets for disorders.

Language: Английский

Citations

7
Molecular overlaps of neurological manifestations of COVID-19 and schizophrenia from a proteomic perspective DOI
André Saraiva Leão Marcelo Antunes, Guilherme Reis‐de‐Oliveira, Daniel Martins‐de‐Souza

et al.

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: July 19, 2024

Language: Английский

Citations

2
Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases DOI Creative Commons

Abudurousuli Adili,

Aerken Dilihumaer,

Huhu Zhu

et al.

Journal of Zhejiang University (Medical Sciences), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Phosphodiesterase (PDE) hydrolyze cyclic adenosine monophosphate (cAMP) and guanosine (cGMP), involve in the regulation of cellular physiological processes neurological functions, including neuronal plasticity, synaptogenesis, synaptic transmission, memory formation cognitive function by catalyzing hydrolysis intracellular cAMP cGMP. A large number basic clinical studies have shown that PDE4 inhibitors block or ameliorate occurrence development central nervous system (CNS) diseases inhibiting hydrolysis, increasing content enhancing its downstream effects. long-term potentiation effect, which can enhance phosphorylation response element binding protein (CREB) upregulate expression related Arc genes hippocampal neurons, thereby improving impairment Alzheimer's disease-like symptoms; also resist Parkinson's disease reducing cytotoxicity induced α-syn effect miR-124-3p on cell activity. Alteration activity is molecular basis psychosis disorders, therefore it considered as one therapeutic targets for schizophrenia. play a role depression; Autism spectrum Huntington's advanced glycation end product receptor (RAGE), TLR4 NLRP3 pathways hippocampus, activation microglia production interleukin-1β, down-regulating HMGB1/RAGE signaling pathway inflammatory factors Increase nociception threshold. might be used treatment fragile X syndrome regulating level affecting mental retardation (FMRP). promote differentiation oligodendrocyte progenitor cells myelination, has potential multiple sclerosis. to Bipolar disorder may targets. At present, several are trials CNS diseases. This article reviews discusses progress researches diseases, providing reference prevention new drugs.

Language: Английский

Citations

1
Putative Pharmacological Depression and Anxiety-Related Targets of Calcitriol Explored by Network Pharmacology and Molecular Docking DOI Creative Commons
Bruna R. Kouba, Glorister A. Altê, Ana Lúcia S. Rodrigues

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(7), P. 893 - 893

Published: July 5, 2024

Depression and anxiety disorders, prevalent neuropsychiatric conditions that frequently coexist, limit psychosocial functioning and, consequently, the individual’s quality of life. Since pharmacological treatment these disorders has several limitations, search for effective secure antidepressant anxiolytic compounds is welcome. Vitamin D been shown to exhibit neuroprotective, antidepressant, properties. Therefore, this study aimed explore new molecular targets calcitriol, active form vitamin D, through integrated bioinformatic analysis. Calcitriol were predicted in SwissTargetPrediction server (2019 version). The disease collected by GeneCards database searching keywords “depression” “anxiety”. Gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) used analyze intersections targets. Network analyses carried out using GeneMania (2023 version) Cytoscape (V. 3.9.1.) software. Molecular docking main network Ligplot intermolecular interactions. Our showed calcitriol may interact with multiple found are receptor (VDR), histamine H3 (H3R), endocannabinoid receptors 1 2 (CB1 CB2), nuclear NR1H3, patched-1 (PTCH1) protein, opioid NOP, phosphodiesterase enzymes PDE3A PDE5A. Considering role pathophysiology depression anxiety, our findings suggest novel putative mechanisms action as well promising whose deserves further investigation.

Language: Английский

Citations

1