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Stress granules: Deciphering the connections to neurodegeneration

 

Featured Speakers: Benjamin Wolozin, MD PhD (Boston University School of Medicine), and Dorothee Dormann, PhD (Johannes Gutenberg University)

Stress granules (SGs) are a type of biomolecular condensate that consist of membraneless compartments formed in cells through liquid–liquid phase separation (LLPS). They have been shown to concentrate proteins such as RNA-binding proteins (RBPs) to enable biochemical reactions. When cells are exposed to acute biotic and abiotic stress, nuclear RBPs translocate to the cytoplasm and nucleate to form SGs and promote cell survival. Mutations in SG proteins, including TIA1, FUS, TDP43, and hnRNPA1, have been observed in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), indicating a potential link between the mechanisms that regulate LLPS and disease progression. Studies suggest that the SG liquid–liquid state undergoes an aberrant phase transition to a more solid-like state, potentially leading to the formation of tau and other protein aggregates. Thus, further understanding of the mechanisms that control LLPS, such as nucleocytoplasmic transport or posttranslational modification, presents a new paradigm for aggregate formation that can lead to new, transformative therapeutics.

During the webinar, viewers will:

  • Learn about different factors influencing SG dynamics,
  • Hear about recently discovered phase separation mechanisms regulating SG proteins implicated in ALS and FTD,
  • Gain insight into the link between SG behavior and neurodegenerative disease.

Want to learn more?