Session: Posters:

Currently, there are no available therapeutics to prevent or slow down the progression of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. Aggregates of disordered proteins are a common pathological feature of these neurodegenerative diseases. The human 20S proteasome mediates the clearance of the aggregate-prone intrinsically disordered proteins (IDPs). Recently, there has been promising evidence that by enhancing the activity of the 20S proteasome offers a possible therapeutic pathway to combat the toxicity associated with these IDP aggregates. Chlorpromazine, an anti-psychotic medication, was identified as a 20S proteasome activator. Through the design and synthesis of Chlorpromazine analogs, potent 20S proteasome activators have been identified that increases the degradation of pathologically relevant IDPs, such as the pathogenic A53T mutated alpha-synuclein in vitro and mammalian cell lines.

Corey Jones

Appearances