Stress granules: emerging players in neurodegenerative diseases

Lin Yuan; Li-Hong Mao; Yong-Ye Huang; Tiago F Outeiro; Wen Li; Tuane C R G Vieira; Jia-Yi Li

doi:10.1186/s40035-025-00482-9

Stress granules: emerging players in neurodegenerative diseases

Transl Neurodegener. 2025 May 12;14(1):22. doi: 10.1186/s40035-025-00482-9.

Authors

Lin Yuan^#¹, Li-Hong Mao^#², Yong-Ye Huang³, Tiago F Outeiro^{4

5

6

7}, Wen Li², Tuane C R G Vieira⁸, Jia-Yi Li^{9

10}

Affiliations

¹ Laboratory of Research in Parkinson's Disease and Related Disorders, Health Sciences Institute, China Medical University, Shenyang, 110122, China. lyuan@cmu.edu.cn.
² Laboratory of Research in Parkinson's Disease and Related Disorders, Health Sciences Institute, China Medical University, Shenyang, 110122, China.
³ College of Life and Health Sciences, Northeastern University, Shenyang, 110169, China.
⁴ Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.
⁵ Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
⁶ Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
⁷ Scientific Employee With an Honorary Contract at Deutsches Zentrum Für Neurodegenerative Erkrankungen (DZNE), Göttingen, Germany.
⁸ Institute of Medical Biochemistry Leopoldo de Meis and National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
⁹ Laboratory of Research in Parkinson's Disease and Related Disorders, Health Sciences Institute, China Medical University, Shenyang, 110122, China. jia-yi.li@med.lu.se.
¹⁰ Neural Plasticity and Repair Unit, Department of Experimental Medical Science Wallenberg Neuroscience Center, BMC, Lund University, 221 84, Lund, Sweden. jia-yi.li@med.lu.se.

^# Contributed equally.

Abstract

Stress granules (SGs) are membraneless organelles formed in the cellular cytoplasm under stressful conditions through liquid-liquid phase separation (LLPS). SG assembly can be both dependent and independent of the eIF2α pathway, whereas cellular protein quality control systems mediate SG disassembly. Chaperones and specific domains of RNA-binding proteins strongly contribute to the regulation SG dynamics. Chronic stress, arising in association with aging, may promote persistent SGs that are difficult to disassemble, thereby acting as a potential pathological nidus for protein aggregation in neurodegenerative diseases (NDDs). In this review, we discuss the dynamics of SGs and the factors involved with SG assembly and disassembly. We also highlight the relationship among LLPS, SGs, and the pathogenesis of different NDDs. More importantly, we summarize SG assembly-disassembly, which may be a double-edged sword in the pathophysiology of NDDs. This review aims to provide new insights into the biology and pathology of LLPS, SGs, and NDDs.

Keywords: Liquid–liquid phase separation; Neurodegenerative disease; RNA-binding protein; Stress granules.

Publication types

Review

MeSH terms

Animals
Cytoplasmic Granules* / metabolism
Humans
Neurodegenerative Diseases* / metabolism
Neurodegenerative Diseases* / pathology
Stress Granules* / metabolism
Stress Granules* / pathology

Abstract

Publication types

MeSH terms

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