RESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-beta plaques and hyperphosphorylated tau proteins, leading to cognitive decline and neuronal death. However, despite extensive research, there are still no effective treatments for this condition. In this study, a series of chloride-substituted Ramalin derivatives is synthesized to optimize their antioxidant, anti-inflammatory, and their potential to target key pathological features of Alzheimer's disease. The effect of the chloride position on these properties is investigated, specifically examining the potential of these derivatives to inhibit tau aggregation and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) activity. Our findings demonstrate that several derivatives, particularly RA-3Cl, RA-4Cl, RA-26Cl, RA-34Cl, and RA-35Cl, significantly inhibit tau aggregation with inhibition rates of approximately 50%. For BACE-1 inhibition, Ramalin and RA-4Cl also significantly decrease BACE-1 expression in N2a cells by 40% and 38%, respectively, while RA-23Cl and RA-24Cl showed inhibition rates of 30% and 35% in SH-SY5Y cells. These results suggest that chloride-substituted Ramalin derivatives possess promising multifunctional properties for AD treatment, warranting further investigation and optimization for clinical applications.
Asunto(s)
Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Proteínas tau , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Humanos , Proteínas tau/metabolismo , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Ácido Aspártico Endopeptidasas/metabolismo , Cloruros/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Agregado de Proteínas/efectos de los fármacos , Línea Celular Tumoral , Antiinflamatorios/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/químicaRESUMEN
BACKGROUND: Noninvasive monopolar radiofrequency (NMRF) is widely used for dermal and subdermal volumetric heating, yet detailed research on its effects on dermal temperature is scarce. AIMS: This study evaluates the impact of NMRF on dermal temperature and its potential for dermal remodeling using a porcine model. METHODS: Noninvasive monopolar radiofrequency was applied to porcine skin with temperature monitoring via optic fiber technology and forward-looking infrared thermal imaging. Safety was evaluated using nitro blue tetrazolium chloride assessments, and effectiveness was determined through histological examinations before and after treatment. RESULTS: Noninvasive monopolar radiofrequency treatment in a porcine model achieved effective dermal remodeling with no thermal damage, recording peak temperatures of 50°C, 60°C, and 70°C. Histological analysis showed increased collagen density, indicating successful tissue remodeling. CONCLUSION: Noninvasive monopolar radiofrequency is effective in delivering controlled dermal heating and enhancing collagen synthesis, promoting safe and efficient skin tightening and dermal remodeling in a porcine model. It presents a viable option for skin rejuvenation therapies.