An expedient synthesis of the indole alkaloid nazlinine is reported. Judicious choice of flow electrochemistry as an enabling technology has permitted the rapid generation of a small library of unnatural relatives of this biologically active molecule. Furthermore, by conducting the key electrochemical Shono oxidation in a flow cell, the loading of electrolyte can be significantly reduced to 20 mol % while maintaining a stable, broadly applicable process.
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http://dx.doi.org/10.1021/ol502201d | DOI Listing |
Background: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Yonsei University, Incheon, Incheon, Korea, Republic of (South).
Background: The accumulation of amyloidogenic proteins is recognized as a primary biomarker, initiator of pathology, and a potential therapeutic target for Alzheimer's disease (AD). An unbiased screening of a small molecule library was conducted to identify new chemical compounds exhibiting amyloid-dissociative properties.
Method: The ability of aryloxypropanolamine derivatives to dissociate amyloid-β (Aβ) aggregates was evaluated through in vitro assays.
Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Focusing on novel AD treatments, the TREAT-AD centers offer an array of free research tools, shared via the AD Knowledge Portal in a Target Enablement Package (TEP). This abstract showcases the research conducted by the IUSM-Purdue TREAT-AD Center, specifically focusing on Targeting class-II PI3K's as a potential breakthrough in AD therapy. Endocytosis within the brain encompasses diverse pathways for internalizing extracellular cargoes and receptors into cells.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug.
View Article and Find Full Text PDFGlob Ment Health (Camb)
January 2025
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Background: While early intervention in psychosis (EIP) programs have been increasingly implemented across the globe, many initiatives from Africa, Asia and Latin America are not widely known. The aims of the current review are (a) to describe population-based and small-scale, single-site EIP programs in Africa, Asia and Latin America, (b) to examine the variability between programs located in low-and-middle income (LMIC) and high-income countries in similar regions and (c) to outline some of the challenges and provide recommendations to overcome existing obstacles.
Methods: EIP programs in Africa, Asia and Latin America were identified through experts from the different target regions.
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