The University of New Mexico

Seminar:

Development of Novel Theranostics for Protein Misfolding Diseases

April 28, 2017

Eva Y. Chi

Aggregation and accumulation of proteins into fibrillar aggregates is a central pathogenic event in neurodegenerative disorders such as Alzheimer’s (AD) and Parkinson’s (PD) diseases. At present, there is no objective test for diagnosing AD or PD, nor can they be prevented or cured. In AD, protein aggregation is believed to initiate a cascade of pathological events, spanning up to two decades, that culminates in neurodegeneration and cognitive decline. Moreover, as therapeutic interventions are more effective in the pre-symptomatic (cognitively normal) phase before significant neuronal loss occurs, protein aggregates are ideal targets for early disease detection and intervention.

We are developing and testing a novel class of oligo(p-phenylene ethynylene) compounds (OPEs) for the simultaneous detection and treatment of protein misfolding diseases. We have shown that anionic OPEs containing ethyl ester functionalized end groups can selectively bind to the fibrillar conformation of proteins and upon binding, exhibit significant increases in fluorescence, making them useful sensors for the optical detection and tracking of amyloids. As OPE fluorescence is coupled to its photosensitization activity, we are currently investigating whether binding concomitantly activates OPE photosensitization to generate singlet oxygens at the amyloid binding site. These powerful oxidizers can subsequently cause oxidative damages to the amyloids and trigger their degradation and clearance from the diseased tissue. Results from this study will enable us to evaluate the feasibility and efficacy of OPEs as theranostics for the early detection and targeted photodynamic therapy treatment of protein misfolding diseases.