SMALL MOLECULE SA-2 USEFUL FOR TREATING ALZHEIMER'S DISEASE

Purpose: Alzheimer's disease (AD) is a neurodegenerative disorder affecting mainly the aged population. Oxidative stress is known to play important role in the pathogenesis of AD and is increased in the brain with aging. Reactive oxygen species (ROS) are released in excess which leads to neuronal atrophy and long-term tissue damage. Low levels of nitric oxide (NO) is beneficial for neurogenesis and has antioxidant activity. Our goal is to synthesize novel hybrid molecules with dual antioxidant-nitric oxide donating activity against oxidative stress-induced hippocampal neuronal HT-22 cell deaths. Method: The compounds (SA-2, SA-9 and SIN-1) were synthesized and encapsulated into nanoparticles (NP). Structure of the compounds and size of nanoparticles were confirmed using 1HNMR and DLS. Mouse HT-22 cells were seeded in 96 well plates, tert-butyl hydrogen peroxide (TBHP,10µM- 5mM) was added and incubated at 2, 4, 6 and 12 hours. MTT assay (Promega) was performed to determine the effective concentration (EC50) of TBHP. For cell viability study cells were treated with/without TBHP and compounds (SA-2, SA-2 NP, SA-9, SIN-1, 1µM, 10 µM and 100 µM). After 6 hours, MTT assay was performed to assess cell proliferation. Results: We found the EC50 of TBHP is 80µM (6h). Compound SA-2 (100µM) and SA-2 NP (0.1%, equivalent to 25µM of free SA-2) provided significant protection to TBHP induced HT-22 cell death. Conclusion: SA-2 NP is highly effective than free SA-2. Further assessments are ongoing.