(Dis)Solving the problem of aberrant protein states

Area of Science:

• Biochemistry
• Molecular Biology
• Neuroscience

Background:

• Protein-misfolding disorders, including neurodegenerative diseases, pose significant therapeutic challenges due to the complex nature of misfolded proteins.
• Effective treatments are scarce, partly because misfolded protein conformers are diverse and difficult to target.

Purpose of the Study:

• To discuss recent advancements in understanding and engineering therapeutic agents for protein-misfolding disorders.
• To highlight the role of liquid-liquid phase separation in protein aggregation and disease pathology.

Main Methods:

• Review of recent scientific literature on protein misfolding, liquid-liquid phase separation, and therapeutic strategies.
• Discussion of the interplay between protein aggregation, phase separation, and disease mechanisms.

Main Results:

• Many aggregation-prone proteins undergo liquid-liquid phase separation, forming distinct cellular condensates.
• Aberrant protein states in these disorders are linked to altered phase separation behaviors.

Conclusions:

• Targeting liquid-liquid phase separation and enhancing proteostasis are promising therapeutic strategies.
• Further research into engineering therapeutic agents for aberrant protein states is crucial for combating protein-misfolding disorders.