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Understanding liquid–liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation
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Understanding liquid–liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation
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Journal Article
Understanding liquid–liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation
2026
Overview
Phase separation is an important process in biology associated with formation of membraneless organelles but possibly related to the emergence of solid inclusions. TDP-43 is a largely studied paradigmatic case, as it forms neuronal cytoplasmic inclusions in neurodegenerative diseases and is an essential component of many membraneless organelles. Here, we review the physicochemical fundamentals of liquid–liquid phase separation (LLPS) of TDP-43 and its fragments in vitro, showing that full-length TDP-43 requires RNA or chaperones to form stable liquid droplets. We describe TDP-43-containing membraneless organelles and the debate on whether these assemblies represent reservoirs for pathological solid inclusion formation.
Publisher
BioMed Central,Springer Nature B.V,BMC
Subject
/ Amyotrophic Lateral Sclerosis - metabolism
/ Animal Genetics and Genomics
/ Animals
/ Biology
/ Biomedical and Life Sciences
/ DNA-Binding Proteins - chemistry
/ DNA-Binding Proteins - metabolism
/ FTLD-TDP
/ Humans
/ Inclusion Bodies - metabolism
/ LATE-NC
/ Lipids
/ Microbial Genetics and Genomics
/ Neurodegenerative Diseases - metabolism
/ Proteins
/ Review
