Small heat shock protein HSPB8 interacts with a pre-fibrillar TDP43 low complexity domain species to delay fibril formation.

ABSTRACT: The loss of cellular proteostasis through aberrant stress granule formation is implicated in neurodegenerative diseases. Stress granules are formed by biomolecular condensation involving protein-protein and protein-RNA interactions. These assemblies are protective, but can rigidify, leading to amyloid-like fibril formation, a hallmark of the disease pathology. Key proteins dictating stress granule formation and disassembly, such as TDP43, contain low-complexity (LC) domains that drive fibril formation. HSPB8, a small heat shock protein, plays a critical role modulating stress granule fluidity, preventing aggregation and promoting degradation of misfolded proteins. We examined the interaction between HSPB8 and the TDP43 LC using thioflavin T (ThT) and fluorescence polarization (FP) aggregat

SUBMITTER: Jami KM 

PROVIDER: S-EPMC11838303 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature