Synaptogyrin 3 Binds Amyloid Beta and May Alter Dopamine Transport in Alzheimer’s Disease
Type of Thesis
Molecular, Cellular, & Developmental Biology
Alzheimer’s Disease effects 35 million elderly individuals globally by causing dementia, memory loss and eventually death. Amyloid Beta (Aß), a neurotropic peptide and a hallmark of AD pathogenesis, disrupts cellular organization and impairs neuronal systems. The dopaminergic system regulates learning, motor function and behavior and malfunctions in early AD. Aß causes dopaminergic transmission to dysfunction by unknown mechanisms. To elucidate these mechanisms, we screened solubilized mouse synaptosomes for proteins that specifically bind Aß 1-42. 107 proteins that bound Aß were identified by mass spectrometry. Human orthologs were further screened in HEK293 cells for Aß binding. Of the thirteen proteins successfully expressed in HEK293 cells, two specifically interacted with Aß 1-42. We selected a synaptic vesicle protein synaptogyrin 3 (SYG3) for further analysis because of its importance in dopaminergic transmission. We show fully purified SYG3 directly binds Aß 1-42, which suggests a role in dopaminergic AD pathogenesis. More research investigating the effects Aß has on SYG3 in cellular and organismal models is required before we can confirm SYG3’s role in AD. We also include a comparative study of SYG3 with other synaptic vesicle proteins and find belief for a conserved Aß binding domain.
Gierach, William, "Synaptogyrin 3 Binds Amyloid Beta and May Alter Dopamine Transport in Alzheimer’s Disease" (2016). Undergraduate Honors Theses. 1270.