Date of Award
Master of Science (MS)
Microbiology, Immunology, and Biochemistry
Jianxiong Jiang, Jeffery D. Steketee
Hippocampus, HSF-BDNF Axis, Molecular Mechanism, Neuroscience, Pharmacology, Riluzole
The FDA-approved amyotrophic lateral sclerosis (ALS) drug Riluzole has great potential in treating Alzheimer’s disease (AD) based on promising animal data as well as its known action on modulating synaptic transmission. However, its detailed mechanism of action is not fully understood. Here, we proposed work aiming to address this aspect via focus- ing on the Heat Shock Factor 1 (HSF1)-dependent mechanisms. We found that Riluzole could increase HSF1 and BDNF (Brain-Derived Neurotrophic Factor) expression both at transcriptional and translational levels. CA1 (Cornu Ammonia, the first region in the hip- pocampal circuit), is its main target. We also demonstrated a protective role of Riluzole on rat primary neuronal culture which was abolished by a HSF1 inhibitor. Current data together suggest that Riluzole’s synaptic-protective mechanism is highly possible through a HSF1-BDNF axis. The positive outcome from this study will facilitate filling our knowl- edge gap and interpretation of the ongoing clinical trials of Riluzole in AD in which the final data will be released later this year.
Zhang, Yi (0000-0001-6872-4281), "Investigation of Riluzole’s Synaptic Protection Mechanism Through HSF1-BDNF Axis" (2019). Theses and Dissertations (ETD). Paper 497. http://dx.doi.org/10.21007/etd.cghs.2019.0490.