One of the most prevalent diseases acquired in older populations and currently the most common form of dementia, exists in the form of Alzheimer's . Progressing over time, Alzheimer's begins intramolecularly through the buildup of amyloid precursor protein derived Aβ peptides which aggregate into neurotoxic fibrils. The fibrils result in damage to memory and cognitive systems, leading to depression of routine function and eventual death. There is currently no cure nor treatment by which this plaque buildup can be prevented or eliminated, and as such, significant work is being made towards this topic. It has been recently discovered that the human matriptase protein is capable of cleaving both the amyloid precursor protein from which Aβ peptides are made as well as the Aβ1-42 peptide itself, facilitating interest into its potential to reduce fibril formation . In this study we set out to determine if the human matriptase serine protease domain can cleave Aβ fibrils or prevent the Aβ fibril formation in vitro. A recombinant matriptase serine protease domain (r-MatPD) was subcloned into a pET-28a-c(+) expressing vector, expressed, and purified via Ni-NTA affinity resin. The purified his-tagged r-MatPD was further auto-activated and incubated with the purified recombinant Aβ1-42 peptides. We observed that r-MatPD can cut polymerized Aβ1-42 into smaller fragments and prevent Aβ1-42 fibril formation. Effectively, this study suggested that the matriptase protease domain can be further investigated for its role in Aβ fibril clearance in vivo with a possibility of developing matriptase therapeutic potentials in treating Alzheimer's patients.
Bachelor of Science (B.S.)
College of Medicine
Length of Campus-only Access
Ruiz, Jonathan D., "Determining the Potential Cleavage of Human Amyloid Beta Fibril Aggregations by the Human Matriptase Serine Protease Domain" (2019). Honors Undergraduate Theses. 779.