Our laboratory is part of the Ann Romney Center for Neurologic Diseases: a group of multidisciplinary biomedical research laboratories which has its central objective in the application of a wide range of current biological methods to the elucidation of the pathogenesis and treatment of certain chronic, unsolved neurological diseases.
Our laboratory is interested in the biochemistry and molecular and cell biology of neuronal degeneration during aging of the mammalian brain, particularly in Alzheimer’s (AD) and Parkinson’s (PD) diseases. The laboratory originally developed methods for the purification and analysis of the intraneuronal paired helical filaments and extra cellular amyloid fibrils that are the hallmarks of the neuropathology of AD.
Extensive studies of the trafficking and processing of the beta-amyloid precursor protein (APP). a type 1 integral membrane glycoprotein critically involved in AD, have been undertaken and continue. The laboratory discovered that Aß is constitutively produced from APP during normal cellular metabolism, enabling dynamic cell biologically studies of the mechanism of Aß production and it’s pharmacological inhibition. The function of APP and the toxic properties of various Aß assemblies on cultured neurons and in relevant mouse models are being examined. The central role of presenilin in APP and Notch signaling and the mechanism by which presenilin mutations produce AD are also under study. Finally, a similar approach is being applied to the function and dysfunction of gene products implicated in PD, particularly a-synuclein and PINK-1. A wide range of methods is employed, including cell culture, protein biochemistry, recombinant DNA studies, immunohistochemistry, light and electron microscopy, and animal modeling.