Annals of Internal Medicine, Journal Year: 2024, Volume and Issue: 177(9), P. JC100 - JC100
Published: Sept. 1, 2024
Meissner WG, Remy P, Giordana C, et al; LIXIPARK Study Group. Trial of lixisenatide in early Parkinson's disease. N Engl J Med. 2024;390:1176-1185. 38598572.
Language: Английский
EClinicalMedicine, Journal Year: 2024, Volume and Issue: 76, P. 102848 - 102848
Published: Sept. 24, 2024
Language: Английский
Citations
28
Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)
Published: Feb. 1, 2025
Abstract INTRODUCTION MicroRNA (miRNA) activity is increasingly appreciated as a key regulator of pathophysiologic pathways in Alzheimer's disease (AD). However, the role miRNAs during progression AD, including resilience and prodromal syndromes such mild cognitive impairment (MCI), remains underexplored. METHODS We performed miRNA‐sequencing on samples posterior cingulate cortex (PCC) obtained post mortem from Rush Religious Orders Study participants diagnosed ante with no (NCI), MCI, or AD. NCI subjects were subdivided low pathology (Braak stage I/II) high III/IV), suggestive resilience. Bioinformatics approaches included differential expression, messenger RNA (mRNA) target prediction, interactome modeling, functional enrichment, AD risk modeling. RESULTS identified specific miRNA groups, mRNA targets, signaling distinguishing resilience, neuropsychological test performance, neuropathological burden, risk. DISCUSSION These findings highlight potential harnessing to manipulate disease‐modifying implications for precision medicine. Highlights (MiRNA) dysregulation well‐established feature Novel also distinguish putative MiRNAs correlate performance burden. Select are associated age significant covariate. MiRNA include insulin, prolactin, kinases, neurite plasticity.
Language: Английский
Citations
1
Pharmacological Research, Journal Year: 2024, Volume and Issue: 207, P. 107312 - 107312
Published: July 18, 2024
Addiction is a chronic relapsing disease with high morbidity and mortality. Treatments for addiction include pharmacological psychosocial interventions; however, currently available medications are limited in number efficacy. The glucagon-like-peptide-1 (GLP-1) system emerging as potential novel pharmacotherapeutic target alcohol other substance use disorders (ASUDs). In this review, we summarize discuss the wealth of evidence from testing GLP-1 receptor (GLP-1R) agonist preclinical models humans ASUDs, possible mechanisms underlying impact GLP-1R agonists on alcohol/substance use, gaps knowledge, future directions. Most research has been conducted relation to use; psychostimulants, opioids, nicotine have also investigated. Preclinical suggests that reduce related outcomes. main proposed reward processing, stress, cognitive function, well broader satiety, changes gastric motility, glucose homeostasis. More in-depth mechanistic studies warranted. Clinical their findings less conclusive; most support safety efficacy ASUD treatment. Identifying preferred compounds, subgroups who responsive some key questions translate promising data into clinical settings. Several trials underway test people ASUDs.
Language: Английский
Citations
6
Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 238 - 238
Published: Feb. 12, 2025
Metabolic diseases like obesity and diabetes are on the rise, therapies with biomacromolecules (such as proteins, peptides, antibodies, oligonucleotides) play a crucial role in their treatment. However, these drugs traditionally injected. For patients chronic (e.g., metabolic diseases), long-term injections accompanied by inconvenience low compliance. Oral administration is preferred, but delivery of challenging due to gastrointestinal barriers. In this article, we introduce available biomacromolecule for treatment diseases. The barriers oral drug strategies overcome also explored. We then discuss alleviating defects, including glucose metabolism, lipid energy such insulin, glucagon-like peptide-1 receptor agonists, proprotein convertase subtilisin/kexin type 9 inhibitors, fibroblast growth factor 21 analogues, peptide YY analogues.
Language: Английский
Citations
0
Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)
Published: Feb. 17, 2025
Abstract Parkinson's disease (PD) is the second most common neurodegenerative disorder. PD patients exhibit varying degrees of abnormal glucose metabolism throughout stages. Abnormal closely linked to pathogenesis and progression. Key processes involved in include transport, glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, pentose phosphate pathway, gluconeogenesis. Recent studies suggest that a potential therapeutic target for PD. In this review, we explore connection between metabolism, focusing on underlying pathophysiological mechanisms. We also summarize drugs related based results from current cellular animal model studies.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2420 - 2420
Published: March 7, 2025
Obesity remains a major epidemic in developed countries, with limited range of effective pharmacological treatments. The modulation PPARα, CB1, or GLP-1 receptor activity has demonstrated beneficial effects, including anti-obesity actions. In this study, we evaluated novel amide derivative oleic acid and tyrosol (Oleyl hydroxytyrosol ether, OLHHA), PPARα agonist, CB1 antagonist, combination the agonist liraglutide (LIG), as an multitarget therapy to improve both peripheral central alterations animal model diet-induced obesity. rats, exposure high-fat high-fructose diet (HFHFD) induced weight gain increased plasma triglycerides, LDL, hepatic parameters. brain, HFHFD provoked disruptions expression proteins regulating food intake, endocannabinoid system, insulin pathway, inflammation resulted altered tau phosphorylation, thus indicating neurodegenerative changes. Based on our results, administration LIG OLHHA alone was insufficient completely reverse noticed at levels. On other hand, combined treatment compounds (OLHHA+LIG) most promoting body loss ameliorating by HFHFDs rats. This therapeutic approach could represent promising strategy for treating obesity associated comorbidities.
Language: Английский
Citations
0
Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 872 - 872
Published: July 19, 2024
Glucagon-like peptide-1 (GLP-1)-based drugs have been approved by the United States Food and Drug Administration (FDA) are widely used to treat type 2 diabetes mellitus (T2DM) obesity. More recent developments of unimolecular peptides targeting multiple incretin-related receptors ("multi-agonists"), including glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) glucagon (Gcg) (GcgR), emerged with aim enhancing drug benefits. In this study, we utilized human mouse microglial cell lines, HMC3 IMG, respectively, together neuroblastoma SH-SY5Y line as cellular models neurodegeneration. Using these studied neuroprotective anti-inflammatory capacity several multi-agonists in comparison a single GLP-1 (GLP-1R) agonist, exendin-4. Our data demonstrate that two selected GLP-1R/GIPR dual agonists GLP-1R/GIPR/GcgR triple agonist not only neurotrophic effects but also anti-neuroinflammatory properties, indicated decreased cyclooxygenase (COX2) expression, nitrite production, pro-inflammatory cytokine release. addition, our results indicate potential outperform commercially available GLP-1R neurodegenerative disease treatment.
Language: Английский
Citations
2
Annals of Internal Medicine, Journal Year: 2024, Volume and Issue: 177(9), P. JC100 - JC100
Published: Sept. 1, 2024
Meissner WG, Remy P, Giordana C, et al; LIXIPARK Study Group. Trial of lixisenatide in early Parkinson's disease. N Engl J Med. 2024;390:1176-1185. 38598572.
Language: Английский
Citations
0