Michael T. Bowers

Research Overview

The Bowers Group research is centered on determing the mechanism of amyloid diseases, especially those involved in aging, and in devloping appropriate therapeutic agants for remediation of these diseases. Historically the work has been focused most intensely on Alzheimer's disease (AD), but recently research programs in both Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease have been initiated. Of particular interest is the cross talk between these diseases that recently has been established by epidemiological evidence. It is known that ALS and AD are coupled in many instances but there has been little detailed evidence of the mechanism of the coupling. One of the most promising areas of research is the Group's discovery that the assembly of crucial "central " peptides often mimic the behavior of the parent protein involved in disease. Hence the assembly and toxicity of the fragment TDP(307-319) in TDP-43, the protein responsible for ALS, mimics the much larger TDP-43 protein that is very difficult to study in detail. It was shown that these critical peptides involved in ALS, AD and Parkinson's disease all form similar structural motifs termed cylindrins; out of register, antiparallel cylic heximers that are the toxic agents in these peptide mimics and are capable of insertion in plasma membranes. When these centrally important peptides are mixed, often strong, catalytic effects are observed on the peptide assembly, often accelerating assembly to the toxic cylindrins in minutes when days or weeks are needed in the neat systems. Finally, in collaboration with Prof. Ambuj Singh in Computer science, small molecule drug candidates are being developed that inhibit toxic oligomer formation, remodel previously formed toxic oligomers to non-toxic small peptides and simultaneously are effective against both AD and ALS. All of these small molecules cross the blood brain barrier, have few side effects and are target specific. Research is on going in these and related areas.