Aberrant liquid-liquid phase separation and amyloid aggregation of proteins related to neurodegenerative diseases

Int J Biol Macromol. 2022 Nov 1:220:703-720. doi: 10.1016/j.ijbiomac.2022.08.132. Epub 2022 Aug 23.

Abstract

Recent evidence has shown that the processes of liquid-liquid phase separation (LLPS) or liquid-liquid phase transitions (LLPTs) are a crucial and prevalent phenomenon that underlies the biogenesis of numerous membrane-less organelles (MLOs) and biomolecular condensates within the cells. Findings show that processes associated with LLPS play an essential role in physiology and disease. In this review, we discuss the physical and biomolecular factors that contribute to the development of LLPS, the associated functions, as well as their consequences for cell physiology and neurological disorders. Additionally, the finding of mis-regulated proteins, which have long been linked to aggregates in neuropathology, are also known to induce LLPS/LLPTs, prompting a lot of interest in understanding the connection between aberrant phase separation and disorder conditions. Moreover, the methods used in recent and ongoing studies in this field are also explored, as is the possibility that these findings will encourage new lines of inquiry into the molecular causes of neurodegenerative diseases.

Keywords: Biomolecular condensates; Liquid-liquid phase separation; Liquid-solid transition; Membrane-less organelles.

Publication types

  • Review

MeSH terms

  • Amyloid / metabolism
  • Amyloidogenic Proteins / metabolism
  • Amyloidosis* / metabolism
  • Humans
  • Neurodegenerative Diseases* / metabolism
  • Organelles / metabolism
  • Phase Transition

Substances

  • Amyloid
  • Amyloidogenic Proteins