Date of Award

8-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biomedical Sciences

Track

Microbiology, Immunology, and Biochemistry

Research Advisor

Liao, Francesca-Fang

Committee

Jianxiong Jiang, Jeffery D. Steketee

Abstract

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.

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

0000-0001-6872-4281

DOI

10.21007/etd.cghs.2019.0490

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