Exploring Human APP/Presenilin-1 Interactions and Wnt signaling in primary neuronal cultures using HSV-1 Based Multigene Delivery

Iliya Lefterov, M.D., Ph.D.
Department of Pharmacology
University of Pittsburgh School of Medicine


Individuals with Alzheimer's disease (AD) are characterized by extensive accumulation of amyloid (a pathologic extracellular protein substance) in the brain, referred to as senile plaques. The specific role of amyloid protein is unclear, but it is thought that amyloid deposits may cause neurons to degenerate.

Dr. Lefterov will study the processing of human amyloid precursor protein (hAPP) into the amyloid peptide _ (A_) that is the major component of senile and cerebrovascular plaques in AD patients. He has found that human bleomycin hydrolase (hBH) (an enzyme) interacts with hAPP as well as with other proteins found in amyloid plaques. Dr. Lefterov will use HSV-1 (herpes simplex virus-type 1) vectors (used to make transfers from one organism to another)
to overexpress hAPP along with PS1 or hBH and study the generation of A_ in rat hippocampal neurons and astrocytes. Dr. Lefterov expects that this study will provide useful preliminary data to support designing molecular and cellular approaches to reveal key aspects of disturbed cell signaling pathways, neurotoxicity, and neuronal death that are considered important in the pathogenesis of AD.