Influence of RhoA and Rac1 Prenylation on Neuroplasticity in Alzheimer’s Disease Models

Alzheimer’s disease (AD) is the sixth leading cause of death in the US and the most common cause of dementia. Statins are drugs that inhibit protein prenylation and are associated with decreased incidence of AD. Guanosine triphosphatase (GTPase) prenylation translocates RhoA and Rac1 to the plasma membrane to affect their activation and neuroplasticity. How this contributes to AD progression is unknown. Previously, RhoA and Rac1 mutants that cannot be prenylated initiate different signaling pathways than the wild-type proteins. This project tests the hypothesis that nonprenylatable RhoA and Rac1 interact with a distinct set of activating guanosine exchange factors (GEFs) to inhibit progression to AD. B35 neuroblastoma cells are transfected with wild-type or non-prenylatable RhoA and Rac1 and their interaction with a panel of GEFs is assessed using western blotting. These studies will identify molecular mechanisms that lead to AD pathology and potentially identify novel targets for new AD treatments.

Presented at the 2021 Student Creative Arts and Research Symposium