Phase Transition of Huntingtin: Factors and Pathological Relevance

Abstract

Formation of intracellular mutant Huntingtin (mHtt) aggregates is a hallmark of Huntington's disease (HD). The mechanisms underlying mHtt aggregation, however, are still not fully understood. A few recent studies indicated mHtt undergoes phase transition, bringing new clues to understand how mHtt aggregates assemble. Here in this mini review, we will summarize these findings with a focus on the factors that affect mHtt phase transition. We will also discuss the possible pathological roles of mHtt phase separation in HD.

Keywords: Huntington’s disease; aggregates; huntingtin; phase separation; phase transition.

FIGURE 1

Liquid-liquid phase separation. A schematic chart of liquid-liquid phase separation (LLPS). In a solution composed of evenly distributed solute molecules (the green bubbles) and solvent molecules (gray bubbles), when LLPS occurs, the solute molecules condense to form a membraneless liquid-like phase and leaves a surrounding region absent of the solute molecules.