Friend or foe: The role of stress granule in neurodegenerative disease

Stress granules (SGs) are dynamic membraneless organelles that form in response to cellular stress. SGs are predominantly composed of RNA and RNA-binding proteins that assemble through liquid-liquid phase separation. Although the formation of SGs is considered a transient and protective response to cellular stress, their dysregulation or persistence may contribute to various neurodegenerative diseases. This review aims to provide a comprehensive overview of SG physiology and pathology. It covers the formation, composition, regulation, and functions of SGs, along with their crosstalk with other membrane-bound and membraneless organelles. Furthermore, this review discusses the dual roles of SGs as both friends and foes in neurodegenerative diseases and explores potential therapeutic approaches targeting SGs. The challenges and future perspectives in this field are also highlighted. A more profound comprehension of the intricate relationship between SGs and neurodegenerative diseases could inspire the development of innovative therapeutic interventions against these devastating diseases.