Highly selective tritiated ligands and autoradiography have been used to study mu and delta binding sites as well as neutral endopeptidase-24.11 in the dorsal horn of the rat spinal cord. Two weeks and 4 months after dorsal root rhizotomy, both opioid binding sites were dramatically decreased (congruent to 60%). In contrast, the level of neutral endopeptidase-24.11 remained unaltered.
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http://dx.doi.org/10.1016/0006-8993(89)91436-4 | DOI Listing |
Background: Genetic studies have established that loss of function SORL1 gene variants are associated with Alzheimer's disease (AD). SORL1 encodes an endosomal trafficking receptor, SORLA, which regulates endosomal protein recycling through its interaction with the retromer core complex (consisting of VPS26, VPS35 and VPS29). Deficits in the levels and function of the SORLA-retromer complex are thought to underlie AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria.
Background: We identified small molecule tricyclic pyrone compound CP2 as a mild mitochondrial complex I (MCI) inhibitor that induces neuroprotection in multiple mouse models of AD. One of the major concerns while targeting mitochondria is the production of reactive oxygen species (ROS). CP2 consists of two diastereoisomers, D1 and D2, with distinct activity and toxicity profiles.
View Article and Find Full Text PDFBackground: Neurological disorders are at epidemic levels in the world today. Various proteins are being targeted for the development of novel molecular therapeutics; however, no small-molecule inhibitors have been discovered. Recent studies suggest that there are few molecules in clinical trials for various secretase (α, β, and γ), caspase, and calpain inhibitors.
View Article and Find Full Text PDFCurr Med Chem
January 2025
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutcihe (STEBICEF) Università di Palermo, Via Archirafi 32, 90123 Palermo.
CDK2 plays a pivotal role in controlling the cell cycle progression in eukaryotes and for this reason, it has been the subject of several studies for suitable inhibitors in the last decades. But more than 30 years of basic research have not generated an inhibitor as marketed drugs. Some inhibitors are to date in early phase clinical development.
View Article and Find Full Text PDFFASEB J
January 2025
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University, Akita, Japan.
Various tubular diseases in patients with multiple myeloma (MM) are caused by monoclonal immunoglobulin light chains (LCs). However, the physicochemical characteristics of the disease-causing LCs contributing to the onset of MM-associated tubular diseases remain unclear. We herein report a rare case of MM-associated combined tubulopathies: non-crystalline light chain proximal tubulopathy (LCPT) and crystalline light chain cast nephropathy (LCCN).
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