Increased attention has been given to the gut lately in a number of conditions, from maintaining health via the use of probiotics to treating Autism Spectrum Disorder. Parkinson's Disease has a history with the gut starting with the Braak hypothesis, in which eminent researcher Heiko Braak observed that the spread of Parkinson's (PD) seemed to occur along either olfactory or enteric neurons prior to reaching the substantia nigra in the midbrain, where the classical disease symptoms become evident. Though this finding was largely ignored at the time, the possibility of a gut origin for PD has received interest lately as a growing body of epidemiological and mechanistic research supports a gut-based influence. One key study showed that the presence of a toxin that induces oxidative stress in the intestine is capable of generating protein aggregates that spread to the brain and cause a PD-like pathology. The spread of protein aggregates from gut neurons to the brain has been corroborated in a number of studies. The open question, then, is what type of toxic triggers are capable of causing protein aggregation in the real world, and how do they cause protein aggregation in enteric neurons, which do not directly contact the intestinal lumen? We propose here that the enzyme Nox1 contributes to oxidative stress in the gut and eventually to the protein aggregation that can lead to PD via the generation of endogenous reactive oxygen species. Nox1 functions to generate superoxide radicals and is highly expressed in the colon. Knockdown of NOX1 in the brain has been shown to have a protective effect in a PD mouse model. To bridge a trigger in the intestinal lumen to protein aggregation in enteric neurons, we investigate a class of cells that contact both the intestinal lumen and enteric neurons, known as enteroendocrine cells. Finally, we conduct a small study to explore a possible toxic trigger, high fat diet.
Bachelor of Science (B.S.)
College of Medicine
Orlando (Main) Campus
Adler, Evan, "Can NoX1 Activity Initiate Parkinson's-Like Pathology in an Enteroendocrine Cell Line?" (2018). Honors in the Major Theses. 406.