Celebrating Scholarship and Creativity Day (2018-)

Document Type

Paper

Publication Date

4-30-2026

Disciplines

Biochemistry, Biophysics, and Structural Biology

Advisor

Dr. Mohamad Ramshan

Abstract

Parkinson's disease (PD) is an advanced neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and the proliferation of protein aggregates within the brain. This capstone thesis investigates the unique biochemical environment of the gastrointestinal tract and whether it contributes to the formation of distinctive α-Synuclein (αSyn) aggregates affecting PD. Key promoters of αSyn aggregation include genetic mutations, oxidative stress, post-translational modifications, interactions with metal ions, and dopamine (DA) oxidation. These factors result in diverse structures such as oligomers, protofibrils, and fibrils, which result in unique functional outcomes, with oligomeric conformations leading to the highest level of neuronal toxicity. Evidence suggests that alternative environments, specifically the gut, likely cause αSyn misfolding, enabling amyloid propagation to the brain, though the biochemical mechanisms remain unclear. This work integrates well-known mechanisms of αSyn aggregation with the emerging gut-origin hypothesis, proposing that unique biochemical environments are responsible for the formation of pathogenic conformations. These findings may lead to earlier detection of PD through gastrointestinal biomarkers and to the development of therapeutic strategies targeting peripheral aggregation before central nervous system (CNS) involvement. This work targets intervention by examining environment-specific mechanisms of disease initiation. Future work will identify the link between peripheral aggregation and disease progression by confirming these mechanisms in more complex biological systems.

Additional Files
Beyond the Brain.pptx (4973 kB)
Download

Share

COinS