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Molecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases.
CNS Neurosci Ther
January 2025
Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, USA.
Introduction: Mitochondrial dysfunction stands as a pivotal feature in neurodegenerative disorders, spurring the quest for targeted therapeutic interventions. This review examines Ubiquitin-Specific Protease 30 (USP30) as a master regulator of mitophagy with therapeutic promise in Alzheimer's disease (AD) and Parkinson's disease (PD). USP30's orchestration of mitophagy pathways, encompassing PINK1-dependent and PINK1-independent mechanisms, forms the crux of this exploration.
View Article and Find Full Text PDFRedefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?
Am J Psychiatry
January 2025
Biobehavioral Imaging and Molecular Neuropsychopharmacology Section, NIDA, Baltimore (Levinstein, Budinich, Michaelides); Department of Pathology and Experimental Therapeutics, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona (Bonaventura); Neuropharmacology and Pain Group, Neuroscience Program, IDIBELL-Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona (Bonaventura); Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford (Schatzberg); Experimental Therapeutics and Pathophysiology Branch, NIMH, Bethesda (Zarate); Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore (Michaelides).
Ketamine is a racemic compound and medication comprised of ()-ketamine and ()-ketamine enantiomers and its metabolites. It has been used for decades as a dissociative anesthetic, analgesic, and recreational drug. More recently, ketamine, its enantiomers, and its metabolites have been used or are being investigated for the treatment of refractory depression, as well as for comorbid disorders such as anxiety, obsessive-compulsive, and opioid use disorders.
View Article and Find Full Text PDFIntranasal racemic ketamine maintenance therapy for patients with treatment-resistant depression: a naturalistic feasibility study.
BMC Psychiatry
January 2025
Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Background: Ketamine is a promising therapy for treatment-resistant depression due to its rapid onset, although benefits are often transitory, with patients needing maintenance therapy to prevent relapse. Most data supporting ketamine for treatment-resistant depression refers to the intravenous route of administration, leaving alternative routes lacking in data, especially as maintenance regimens. Moreover, the safety of ketamine maintenance therapy is poorly defined.
View Article and Find Full Text PDFSynthesis and LDHA Inhibitory Activity of New Stiripentol-Related Compounds of Potential Use in Primary Hyperoxaluria.
Int J Mol Sci
December 2024
Department of Inorganic and Organic Chemistry, Faculty of Experimental Sciences, University of Jaén, Campus of International Excellence in Agri-Food (ceiA3), 23071 Jaén, Spain.
Human lactate dehydrogenase A (LDHA) is a homotetrameric isozyme involved in the conversion of glyoxylate into oxalate in the cytosol of liver cells (hepatocytes) and partially responsible for the overproduction of oxalate in patients with the rare disease called primary hyperoxaluria (PH). Recently, LDHA inhibition has been validated as a safe therapeutic method to try to control the PH disease. Stiripentol (STP) is an approved drug used in the treatment of seizures associated with Dravet's syndrome (a severe form of epilepsy in infancy) which, in addition, has been drawing interest in recent years also for potentially treating PH, due to its LDHA inhibitory activity.
View Article and Find Full Text PDFKetamine Reduces Avoidance Responses During Re-Exposition to Aversive Stimulus: Comparison Between ()-Isomer and Racemic Mixture.
Brain Sci
December 2024
Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal 59078-900, Brazil.
Background/objectives: Recent studies have investigated the effects of ketamine on fear memory in animals. However, it is unclear if ketamine might affect avoidance memory and emotional behaviors concomitantly. In this study, we compared the effects of (,)- and ()-ketamine in modulating avoidance responses, depression- and anxiety-related behaviors in stressed mice.
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