LLPS and phase transition (LLPT) of proteins and nucleic acids have become a new research direction in cell biology. Because of the occurrence of many diseases is closely related to the liquid-solid phase transition process of protein and lipid production, such as Parkinson’s disease dementia (PDD).
Through kinetic and thermodynamic ways, they undergo the liquid-solid phase transition to produce a liquid condensate that can mature and solidify, forming a structure similar to amyloid fibrin, and reaching an irreversible and more stable state. Specifically, the viscosity and rigidity of these dynamic droplets increase over time. Biological macromolecules can be condensed into membrane-free condensates like liquid through liquid-liquid phase separation (LLPS). Several research results present show that phase separation generally exists in proteins, lipids, and other substances and participates in physiological and pathological processes by changing the state of substances. In the early stage, phase separation or phase transition was applied as a physical and chemical concept to explain the separation of mixed liquids, which was extended as a biological concept to study the occurrence and development of diseases. Determining the significance of LLPS in neurodegenerative diseases such as PDD will stimulate interest in research into treatments based on interference with abnormal LLPS.
Therefore, we believe that LLPS can serve as one of the means to explain the pathological mechanism of PDD. By analyzing the existing literature, we propose that LLPS is the crucial mechanism causing abnormal accumulation of α-syn, tau, and other proteins in PDD, and its interaction with iron metabolism disorder is the key factor driving ferroptosis in PDD. Substances such as proteins can form droplets through liquid-liquid phase separation (LLPS) under normal physiological conditions and even undergo further liquid-solid phase transitions to form solid aggregates under disease or regulatory disorders, leading to pathological phenomena. Studies have shown that the occurrence and development of neurodegenerative diseases such as PDD are closely related to the separation of abnormal phases. However, the links and mechanisms between these factors remain unclear. The interaction of iron accumulation with α-syn and tau was further explored as an essential pathological mechanism of PDD. The pathological features of PDD are represented by dopaminergic neuronal death and intracellular α-synuclein ( α-syn) aggregation.
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