P002 - HYDROXYPROPYL-METHYLCELLULOSE DERIVATIVE PREVENTS AMYLOID-BETA ACCUMULATION, NEUROINFLAMMATION, AND APOPTOTIC NEURODEGENERATION IN A MOUSE MODEL OF ALZHEIMER’S DISEASE
Abstract
Aims
Polysaccharides such as cellulose ether (CE) formulations are emerging as potential therapeutics for neurodegenerative diseases associated with protein misfolding. The main objective of our study was to test the therapeutic effects of the CE (TC-5RW), a modified hydroxypropyl-methylcellulose in the 5xFAD transgenic mouse model of Alzheimer’s disease (AD).
Methods
Two groups of 5xFAD mice were used, one group was treated with only a single subcutaneous dose of TC-5RW (4g/kg) at the age of 6 weeks. Mice of both groups were sacrificed at 10 months and brains were collected for immunoblotting and confocal microscopy analyses of Aβ, GFAP and caspase-3. Additionally, we applied Thioflavin-T assay to analyse Ab aggregation kinetics, and tested Ab toxicity on mouse neuroblastoma (N2a) cells by MTT assay.
Results
The immunoblotting results revealed that TC-5RW reduced the Aβ level in the brain homogenates of TC-5RW-treated 5xFAD mice compared to control 5xFAD mice. Interestingly, the immunofluorescence assay using Aβ6E10 antibody further indicated that TC-5RW reduced the Aβ plaque burden in the hippocampi and cortical tissues. TC-5RW attenuated astrogliosis in hippocampi and cortical tissues, shown by analysis of GFAP reactivity. Furthermore, reduced levels of caspase-3 were found by immunoblot in brain homogenates of TC-5RW treated mice, indicating alleviation of apoptotic neurodegeneration compared to control 5xFAD mice. The in vitro Thioflavin-T and MMT results indicated that TC-5RW inhibited Aβ aggregation and toxicity.
Conclusions
Overall, our in vivo and in vitro results suggest that CE based compounds might be valuable and emerging therapeutics for the prevention and treatment of AD.
