Liquid-Liquid Phase Separation (LLPS) plays a crucial role in the assembly and regulation of inflammatory signalling ensembles. LLPS is a phenomenon where biomacromolecules, such as proteins and RNA, separate from a homogeneous solution, and form distinct liquid droplets or condensates. These condensates can orchestrate various cellular processes. LLPS can modulate signalling pathways by creating distinct microenvironments that facilitate or inhibit protein-protein interactions. Misfolding and aggregation of specific proteins associated with LLPS can interfere with normal cellular functions, and lead to various forms of cell death. Aberrant LLPS has now been linked to various diseases, including hypersensitivity reactions, and autoimmune disorders. Researchers are nowadays exploring ways to disrupt LLPS, which could potentially treat such diseases associated with aberrant phase separation. Pharmacological targeting of LLPS is thus becoming a promising area of research, with LLPS based therapies modulating immunological crosstalk and signal transduction, having potential applications in treating various disorders. Pathological condensates can be disrupted by reducing multivalency with selective inhibitors or using small molecule drugs to reverse solidification. To overcome the high concentration requirements for dissolution, nanomedicine is essential. Nanoparticle encapsulated drug can ensure precise delivery and high local payloads, effectively dissolving these condensates. This review highlights the biophysical and biochemical aspects of phase separation and biomolecular condensate formation, and how understanding of their components and mechanisms can be leveraged to develop therapeutic strategies against pathological immunological condensates.
Sarkar et al. (Thu,) studied this question.
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