New low-dose curcumin derivative with therapeutic potential in Alzheimer’s disease: Results from an in vitro and in vivo study in mice

• DOI: 10.1016/j.neurobiolaging.2024.12.005
• Publication Date: 2024-12-21T07:30:48Z
• Authors: Beatriz Rodrigues; Eduarda Ventura; Patrícia Moreira; Rosa Resende; Joana Bicker; Armanda E. Santos; Cláudia Fragão Pe...; Maria Teresa Cruz; Maria Paula Robalo; Ana Silva; Sónia Silva

Curcumin has been proposed as a potential treatment for Alzheimer's disease (AD) due to its ability inhibit amyloid-β (Aβ) peptide aggregates and destabilise pre-formed ones. Derivative 27 was synthesized improve low-dose efficacy in the context of AD. Its anti-inflammatory, antioxidant anti-amyloidogenic activities were evaluated chemico, vitro using AD neuroinflammation cell models, vivo double-transgenic APP/PS1 mice. In vitro, this curcumin derivative significantly reduced nitric oxide (NO) production levels pro-inflammatory proteins, inducible NO synthase, pro-interleukin-1β (Pro-IL-1β) cyclooxygenase-2. Furthermore, activated nuclear factor erythroid 2-related 2 transcription (Nrf2) increased Nrf2 heme-oxygenase-1 protein nucleus cytoplasm, respectively. one-year-old mice, orally administered-Derivative (50 mg/Kg/day) 28 days improved spatial short-term memory decreased hippocampal Pro-IL-1β amyloid precursor levels, well Aβ hippocampus plasma. This study supports developing new chemical approaches alter molecule, enabling lower doses, while increasing effectiveness treatment.