Program
Biomedical Engineering
College
Engineering
Student Level
Doctoral
Start Date
7-11-2019 4:00 PM
End Date
7-11-2019 5:00 PM
Abstract
Alzheimer's disease (AD) is the 6th leading cause of death in the U.S. and the only disease in the top ten causes for which we have no treatment or cure. The cost of this disease is expected to rise over a trillion dollars over the next 30 years, it affects individuals and it is also a national healthcare crisis. This disease shares pathological hallmarks, protein aggregates, with other neurodegenerative disorders such as Parkinson's disease and traumatic brain injuries. Proteins are an organism's micro-machinery for transport, defense, storage, and communication. However, in neurodegenerative diseases, the proteins malfunction, change shape, clump together and cause damage to neurons resulting in cell death. Such protein aggregates are characterized by the misfolding and aggregation of the amyloid beta (A) and tau proteins in AD. Neuronal loss occurs decades prior to the onset of symptoms, making the pre-symptomatic stage an ideal target window for detection and treatment. Currently, we do not have clinically useful diagnostic tools to detect these biomarkers. Oligo phenylene ethynylenes (OPEs) are a novel class of molecular sensors with turn-on fluorescence mechanisms. A library of OPEs includes molecules varying in lengths, charges, and chemical groups. We have narrowed the selection down to two molecules with opposite charges. These two OPES display high selectivity for the pathological fibrillar form of protein versus a healthy, monomeric protein. While the molecules are non-fluorescent in water, they become super-luminescent after binding to their target, large protein assemblies. Our idea revolves around the application of OPEs as a non-protein specific, aggregate specific, biological sensors for pathological protein aggregates. We have tested the selectivity and affinity of these sensors towards protein assemblies in animal and human brain tissue with optimistic results. Due to this, we see the potential of these small molecules as diagnostic tools for neurodegeneration or other diseases also characterized by unhealthy protein aggregation such as systemic amyloidosis or type II diabetes.
Novel Biological Super-Luminescent Sensors for the Detection of Neurodegenerative Disorders
Alzheimer's disease (AD) is the 6th leading cause of death in the U.S. and the only disease in the top ten causes for which we have no treatment or cure. The cost of this disease is expected to rise over a trillion dollars over the next 30 years, it affects individuals and it is also a national healthcare crisis. This disease shares pathological hallmarks, protein aggregates, with other neurodegenerative disorders such as Parkinson's disease and traumatic brain injuries. Proteins are an organism's micro-machinery for transport, defense, storage, and communication. However, in neurodegenerative diseases, the proteins malfunction, change shape, clump together and cause damage to neurons resulting in cell death. Such protein aggregates are characterized by the misfolding and aggregation of the amyloid beta (A) and tau proteins in AD. Neuronal loss occurs decades prior to the onset of symptoms, making the pre-symptomatic stage an ideal target window for detection and treatment. Currently, we do not have clinically useful diagnostic tools to detect these biomarkers. Oligo phenylene ethynylenes (OPEs) are a novel class of molecular sensors with turn-on fluorescence mechanisms. A library of OPEs includes molecules varying in lengths, charges, and chemical groups. We have narrowed the selection down to two molecules with opposite charges. These two OPES display high selectivity for the pathological fibrillar form of protein versus a healthy, monomeric protein. While the molecules are non-fluorescent in water, they become super-luminescent after binding to their target, large protein assemblies. Our idea revolves around the application of OPEs as a non-protein specific, aggregate specific, biological sensors for pathological protein aggregates. We have tested the selectivity and affinity of these sensors towards protein assemblies in animal and human brain tissue with optimistic results. Due to this, we see the potential of these small molecules as diagnostic tools for neurodegeneration or other diseases also characterized by unhealthy protein aggregation such as systemic amyloidosis or type II diabetes.
