2023 FDA TIDES (Peptides and Oligonucleotides) Harvest

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 243 - 243

Published: Feb. 13, 2024

A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four oligonucleotides are indicated for various types disorders, including amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, polyneuropathy hereditary transthyretin-mediated amyloidosis. All show chemically modified structures to enhance their stability therapeutic effectiveness as antisense or aptamer oligomers. Some them demonstrate conjugation driving ligands. peptides comprise structures, linear, cyclic, lipopeptides, have diverse applications. Interestingly, has granted its first orphan drug designation a peptide-based highly selective chemokine antagonist. Furthermore, Rett syndrome found first-ever core symptoms treatment, which is also peptide-based. Here, we analyze in 2023 on basis chemical structure, medical target, mode action, administration route, common adverse effects.

Language: Английский

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Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 108 - 108

Published: Jan. 18, 2025

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation reactive oxygen species (ROS), calcium homeostasis, and execution apoptotic processes. Disruptions function, driven by factors such as oxidative stress, excitotoxicity, altered ion balance, lead to neuronal death contribute cognitive impairments several brain diseases. Mitochondrial can arise from genetic mutations, ischemic events, hypoxia, other environmental factors. This article highlights critical role progression diseases discusses need targeted therapeutic strategies attenuate damage, restore enhance neuroprotection.

Language: Английский

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Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 5, 2025

The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. integration novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, artificial intelligence have significantly expedited the development groundbreaking drugs, effectively addressing obstacles associated with their character, such as rapid clearance degradation, necessitating subcutaneous injection leading increasing patient discomfort, ultimately advancing translational research efforts. Peptides are presently employed in management diagnosis diverse array medical conditions, diabetes mellitus, weight loss, oncology, rare diseases, additionally garnering interest facilitating targeted platforms advancement vaccines. This paper provides an overview present market clinical trial progress therapeutics, platforms, It examines key areas through literature analysis emphasizes structural modification principles well recent advancements screening, design, technologies. accelerated including peptide-drug complexes, new vaccines, innovative diagnostic reagents, has potential promote era precise customization disease therapeutic schedule.

Language: Английский

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Role of calcium overload-mediated disruption of mitochondrial dynamics in offspring neurotoxicity due to methylmercury exposure during pregnancy and lactation

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 291, P. 117835 - 117835

Published: Feb. 1, 2025

Language: Английский

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Polydatin reactivates mitochondrial bioenergetics and mitophagy while preventing premature senescence by modulating microRNA-155 and its direct targets in human fibroblasts with trisomy 21

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Mitochondrial dysfunction and redox dyshomeostasis are considered crucial factors causally linked to the pathogenesis of Down syndrome (DS), a human genetic anomaly currently lacking cure, associated with neurodevelopmental deficits in children early onset symptoms aging adults. Several natural plant-derived polyphenolic compounds, known for their neurostimulator, antioxidant anti-inflammatory activities, have been proposed as dietary supplements manage DS-linked phenotypic alterations. However, poor bioavailability rapid metabolism these compounds limited conclusive evidence regarding clinical efficacy individuals DS. Polydatin (PLD), glucoside precursor resveratrol derived from Polygonum cuspidatum, is instead highly bioavailable resistant enzymatic oxidation. PLD supplementation has shown many therapeutic efficacies several diseases without side effects. In this study, we used fetal trisomy 21 skin fibroblasts (DS-HSFs) investigate, mechanistic point view, whether could prevent or counteract critical cellular alterations both Our findings demonstrate that reactivates mitochondrial bioenergetics, reduces oxygen radical overproduction prevents oxidative stress (OS)-induced senescence DNA damage DS-HSF. Notably, identified novel mechanism action involving chromosome-21-encoded microRNA-155 (miR-155) its direct target genes casitas B-lineage lymphoma (CBL), BAG Cochaperone 5 (BAG5) transcription factor A (TFAM). These proteins play pivotal roles regulating biogenesis mitophagy. Given deregulation miR-155/CBL axis also implicated acute leukemias, which frequently occur DS, emerges promising candidate translational application. Its ability enhance bioenergetics address DS-associated highlights potential.

Language: Английский

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PGC-1α integrates insulin signaling with mitochondrial physiology and behavior in a Drosophila model of Fragile X Syndrome

npj Metabolic Health and Disease, Journal Year: 2024, Volume and Issue: 2(1)

Published: Feb. 21, 2024

Abstract Fragile X Syndrome (FXS) is the most prevalent monogenetic form of intellectual disability and autism. Recently, dysregulation insulin signaling (IS) aberrations in mitochondrial function have emerged as robust, evolutionarily conserved components FXS pathophysiology. However, mechanisms by which altered IS dysfunction impact behavior context remain elusive. Here, we show that normalization improves volume flies lack expression dfmr1 , Drosophila homolog causal gene humans. Further, demonstrate underlies diminished master regulator PGC-1α/Spargel mutant flies. These results are behaviorally relevant, pan-neuronal augmentation circadian mutants. Notably, also modulation wild-type phenocopies defect. Taken together, presented herein provide a mechanistic link between both pathogenesis well more broadly at interface metabolism behavioral output.

Language: Английский

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Biomaterials targeting the microenvironment for spinal cord injury repair: progression and perspectives

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: May 9, 2024

Spinal cord injury (SCI) disrupts nerve pathways and affects sensory, motor, autonomic function. There is currently no effective treatment for SCI. SCI occurs within three temporal periods: acute, subacute, chronic. In each period there are different alterations in the cells, inflammatory factors, signaling spinal cord. Many biomaterials have been investigated of SCI, including hydrogels fiber scaffolds, some progress has made using multiple materials. However, limitations when individual treatment, these can be significantly improved by combining treatments with stem cells. order to better understand investigate new strategies its several combination therapies that include materials combined drugs, cytokines, etc. summarized current review.

Language: Английский

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Trofinetide—a new chapter in rett syndrome’s treatment

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

Published: Nov. 16, 2023

Trofinetide is the first drug approved by FDA to treat Rett Syndrome in children aged 2 years or above. The significantly improved syndrome behavioral scores questionnaire clinical studies. Although further research needed assess potential adverse events, Trofinetide's notable efficacy signifies a significant advancement treatment, offering new therapeutic avenue with ameliorate condition.

Language: Английский

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Pharmacological inhibition of the CB1 cannabinoid receptor restores abnormal brain mitochondrial CB1 receptor expression and rescues bioenergetic and cognitive defects in a female mouse model of Rett syndrome

Molecular Autism, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 19, 2024

Defective mitochondria and aberrant brain mitochondrial bioenergetics are consistent features in syndromic intellectual disability disorders, such as Rett syndrome (RTT), a rare neurologic disorder that severely affects mainly females carrying mutations the X-linked MECP2 gene. A pool of CB1 cannabinoid receptors (CB1R), primary receptor subtype endocannabinoid system brain, is located on membranes (mtCB1R), where it can locally regulate energy production, synaptic transmission memory abilities through inhibition intra-mitochondrial protein kinase (mtPKA). In present study, we asked whether an overactive mtCB1R-mtPKA signaling might underlie alterations RTT its modulation by systemic administration CB1R inverse agonist rimonabant improve cognitive defects mice modeling RTT.

Language: Английский

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Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 203, P. 106726 - 106726

Published: Nov. 5, 2024

The finely tuned regulation of mitochondria activity is essential for proper brain development. Fragile X Syndrome (FXS), the leading cause inherited intellectual disability, a neurodevelopmental disorder in which mitochondrial dysfunction has been increasingly implicated. This study investigates role Glycogen Synthase Kinase 3β (GSK3β) FXS. Several studies have reported dysregulation GSK3β FXS, and its function also well established. However, link between disrupted FXS remains unexplored. Utilizing Fmr1 knockout (KO) mice human cell lines from individuals with we uncovered developmental window where dysregulated disrupts function. Notably, partial inhibition fibroblasts young rescues observed defects, suggesting that targeting early stages may offer therapeutic benefits this condition.

Language: Английский

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