Aberrant protein folding is severely problematic and manifests in numerous disorders, including amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), Huntington disease (HD), and Alzheimer disease (AD).
Patients with each of these disorders are characterized by the accumulation of mislocalized protein deposits. Treatments remain palliative, and no available therapeutic eliminates the underlying toxic conformers.
An intriguing approach to reverse deleterious protein misfolding is to upregulate chaperones to restore proteostasis. Dr. Shorter and his team recently re-engineered a prion disaggregase from yeast, Hsp104, to reverse protein misfolding implicated in human disease. These potentiated Hsp104 variants suppress TDP-43, FUS, and α-synuclein toxicity in yeast, eliminate aggregates, reverse cellular mislocalization, and suppress dopaminergic neurodegeneration in an animal model of PD.
- Reverses of protein aggregation
- Restores protein function, ie, normal functionality
Stage of Development:
In vivo experiments
Jackrel, MR et al.; Cell 2014 Jan 156(1-2) 170
- Sponsored research
Docket # 14-7014