Investigation of Lactocaseibacillus rhamnosus HA-114 and its underlying mechanisms as therapeutics for neurodegeneration
Many studies suggest that genes, environment, and age contribute to the onset of late-life neurodegenerative disease like amyotrophic lateral sclerosis. Epidemiological studies have shown correlations between environmental chemical exposure and neurodegeneration, but no direct and causal relationships have been established. Conversely, there may be environmental actors that suppress or delay neurodegeneration outcomes. The human body is the natural habitat for many microbes, including hundreds of bacterial species referred to as the microbiota. A growing body of work suggests that gut microbiota has a profound effect on health including for neurodegenerative diseases. Our laboratory uses the nematode C. elegans, and its genetic methodologies to model aspects of human neurodegenerative diseases. As part of previous therapeutic discovery program, findings from our worm model have been successfully translated to preclinical and clinical settings for human neurodegenerative disorders. We discovered a probiotic bacteria strain that suppresses neurodegeneration in C. elegans models of ALS. Using a combination of chemical-genetic approaches we propose to identify the neuroprotective molecules originating with the probiotic bacteria, and the genes and pathways essential for suppressing neurodegeneration in our C. elegans models. Along this project, we will explore whether homologue key molecules can be identified and validated in more advanced vertebrate.