A novel drug target to prevent the protein aggregation in neurodegenerative diseases

The accumulation of protein aggregates in the brain in a hallmark of neurodegenerative diseases (NDs) in aging. Protein aggregation of NDs, including Alzheimer disease (AD), Huntington disease (HD), Parkinson disease (PD), and Amyotrophic Lateral Sclerosis (ALS), share a common denominator, production of abnormal proteins, which is one of the main factors to promote NDs. The Miao lab has been studying the molecular mechanisms of the in vivo protein aggregation formation for NDs.

Using interdisciplinary approaches, we identified multiple cellular pathways that prevent the formation of the protein aggregation or reverse the formed aggregates into soluble monomers. Using a single-cell eukaryote, budding yeast, which is one of the best powerful aging study models, we identified a chaperonin protein that is highly involved in the formation of protein aggregates of multiple NDs. One of the novel previously uncharacterized chaperonin protein, chaperonin H, showed extremely high potent for the prevention of protein aggregation of amyloids of Alzheimer's disease.

In addition, from our in vivo cell biology assays we found this previously unidentified chaperonin H showed a broader effect in preventing the formation of multiple types of protein aggregates, including the deleterious proteins of AD, HD, PD, and AHL. The proposed research will have a focused study in understanding the molecule mechanisms by which this previously overlooked chaperonin H has such strong potent against protein aggregation in neurodegeneration. Integrated cell biology, biochemical activity study, and structural biology approaches will be used to perform an in-depth study and in developing a high potential preventive and protective medicine in neurodegeneration.