Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology, Journal Year: 2023, Volume and Issue: 17(4), P. 249 - 263
Published: Dec. 1, 2023
Language: Английский
Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(9), P. 1283 - 1283
Published: Sept. 11, 2023
The processes used by academic and industrial scientists to discover new drugs have recently experienced a true renaissance, with many exciting techniques being developed over the past 5-10 years alone. Drug design discovery, search for safe well-tolerated compounds, as well ineffectiveness of existing therapies, society's insufficient knowledge concerning prophylactics pharmacotherapy most common diseases today, comprise serious challenge. This can influence not only quality human life, but also health whole societies, which became evident during COVID-19 pandemic. In general, process drug development consists three main stages: preclinical using cell-based animal models/tests, clinical trials on humans and, finally, forward moving toward step obtaining regulatory approval, in order market potential drug. this review, we will attempt outline first important consecutive phases development, based experience cooperating complementary centers Visegrád group; i.e., Medical University Lublin, Poland, Masaryk Brno, Czech Republic, Comenius Bratislava, Slovak Republic.
Language: Английский
Citations
28
Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114710 - 114710
Published: May 3, 2023
α-Mangostin (α-MG) is a natural xanthone obtained from the pericarps of mangosteen. It exhibits excellent potential, including anti-cancer, neuroprotective, antimicrobial, antioxidant, and anti-inflammatory properties, induces apoptosis. α-MG controls cell proliferation by modulating signaling molecules, thus implicated in cancer therapy. possesses incredible pharmacological features modulates crucial cellular molecular factors. Due to its lesser water solubility pitiable target selectivity, has limited clinical application. As known gained significant attention scientific community, increasing interest extensive technical biomedical applications. Nanoparticle-based drug delivery systems were designed improve efficiency α-MG. This review focused on recent developments therapeutic potential managing neurological diseases, with special focus mechanism action. In addition, we highlighted biochemical features, metabolism, functions, anti-inflammatory, antioxidant effects pre-clinical applications
Language: Английский
Citations
27
Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)
Published: Nov. 19, 2024
Abstract Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons poses great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it urgent need explore other potential mechanism develop novel approach delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), versatile epigenetic regulators responsible gene transcription via binding histones or non-histone substrates, have grabbed considerable attention in drug discovery. There also substantial evidences supporting aberrant expressions and/activities HDAC isoforms reported epilepsy inhibitors (HDACi) been purposes this condition. However, specific mechanisms underlying role HDACs progression not fully understood. Herein, we reviewed basic information HDACs, summarized recent findings associated with roles diverse subunits discussed regulatory which affected development epilepsy. Additionally, provided brief discussion on as promising targets treatment, serving valuable reference study clinical translation field.
Language: Английский
Citations
14
Molecular Aspects of Medicine, Journal Year: 2022, Volume and Issue: 88, P. 101157 - 101157
Published: Nov. 29, 2022
Vision impairment has devastating consequences for the quality of human life. The cells and tissues associated with visual process must function throughout one's life span maintain homeostasis despite exposure to a variety insults. Maintenance proteome is termed proteostasis, vital normal cellular functions, especially at an advanced age. Here we describe basic aspects from protein synthesis folding degradation, discuss current status field particular focus on major age-related eye diseases: macular degeneration, cataract, glaucoma. Our intent allow vision scientists determine where how harness proteostatic machinery extending functional in aging retina, lens, trabecular meshwork. Several common themes have emerged these having vastly different metabolisms. Continued insults, including chronic stress advancing age, increases burden reduces fidelity degradation machineries ubiquitin-proteasome autophagy-lysosome systems that recognize remove damaged proteins. This "double jeopardy" results exponential accumulation cytotoxic proteins We conclude discussion challenges maintaining appropriate balance pathways, suggest harnessing capacities should provide new opportunities design interventions attenuating diseases before they limit sight.
Language: Английский
Citations
32
Molecules, Journal Year: 2023, Volume and Issue: 28(9), P. 3698 - 3698
Published: April 25, 2023
Cancer treatments with targeted therapy have gained immense interest due to their low levels of toxicity and high selectivity. Proteolysis-Targeting Chimeras (PROTACs) drawn special attention in the development cancer therapeutics owing unique mechanism action, ability target undruggable proteins, focused engagement. PROTACs selectively degrade protein through ubiquitin-proteasome system, which describes a different mode action compared conventional small-molecule inhibitors or even antibodies. Among types, prostate (PC) is most prevalent non-cutaneous men. Genetic alterations overexpression several genes, such as FOXA1, AR, PTEN, RB1, TP53, etc., suppress immune response, resulting drug resistance drugs cancer. Since progression ARV-110 (PROTAC for PC) into clinical phases, focus research has quickly shifted degraders targeting The present review highlights an overview superiority over inhibitors. We also delve underlying pathophysiology disease explain structural design linkerology strategies PROTAC molecules. Additionally, we touch on various targets cancer, including androgen receptor (AR) other critical oncoproteins, discuss future prospects challenges this field.
Language: Английский
Citations
19
Drug Discovery Today, Journal Year: 2022, Volume and Issue: 27(10), P. 103305 - 103305
Published: June 18, 2022
Language: Английский
Citations
24
Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(5), P. 1748 - 1777
Published: April 29, 2023
Abstract Parkinson's disease (PD) is a multifactorial due to complex interplay between genetic and epigenetic factors. Recent efforts shed new light on the mechanisms involved in regulating pathways related development of PD, including DNA methylation, posttranslational modifications histones, presence microRNA (miRNA or miR). Epigenetic regulators are potential therapeutic targets for neurodegenerative disorders. In review, we aim summarize regulation describe how methyltransferases, histone deacetylases, acetyltransferases that mediate key processes PD attractive targets. We discuss use inhibitors and/or activators these models patients, small molecule modulators elicit neuroprotective effects. Further more, given importance miRNAs their contributions underlying will be discussed as well, together with miRNA‐based therapies.
Language: Английский
Citations
17
Bioorganic & Medicinal Chemistry Letters, Journal Year: 2022, Volume and Issue: 76, P. 129015 - 129015
Published: Oct. 5, 2022
Language: Английский
Citations
23
Brain Sciences, Journal Year: 2022, Volume and Issue: 12(5), P. 672 - 672
Published: May 21, 2022
Parkinson’s disease (PD) is a chronic progressive neurodegenerative that increasingly becoming global threat to the health and life of elderly worldwide. Although there are some drugs clinically available for treating PD, these treatments can only alleviate symptoms PD patients but cannot completely cure disease. Therefore, exploring other potential mechanisms develop more effective modify course still highly desirable. Over last two decades, histone deacetylases, as an important group epigenetic targets, have attracted much attention in drug discovery. This review focused on current knowledge about deacetylases involved pathophysiology their inhibitors used studies. Further perspectives related small molecules inhibit or degrade treat were also discussed.
Language: Английский
Citations
22
Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 206, P. 115295 - 115295
Published: Oct. 12, 2022
Language: Английский
Citations
21