Relation Between Stress Granules and Cytoplasmic Protein Aggregates Linked to Neurodegenerative Diseases

• Published in: Current neurology and neuroscience reports Vol. 18; no. 12; pp. 107 - 9
• Main Authors: Dobra, Ioana, Pankivskyi, Serhii, Samsonova, Anastasiia, Pastre, David, Hamon, Loic
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2018; Springer Nature B.V; Current Medicine Group
• Subjects: Alternative splicing; Cytoplasm; Environmental stress; Genetics (V Bonifati; Life Sciences; Life span; Medicine; Medicine & Public Health; Metabolism; Neurodegenerative diseases; Neurology; Neurons; Neurosciences; Protein interaction; Protein sources; Proteins; RNA transport; RNA-binding protein; Section Editor; Seeds; Topical Collection on Genetics; Compartmentalization; Neurodegenerative disease; RNA-binding protein; Liquid-liquid phase separation; Stress granules; Low complexity domain
• ISSN: 1528-4042; 1534-6293; 1534-6293
• DOI: 10.1007/s11910-018-0914-7

ᅟ A hallmark of neurodegenerative diseases is the accumulation of cytoplasmic protein aggregates in neurons of affected subjects. Among recently identified elements of these aggregates are RNA-binding proteins (RBPs) involved in RNA metabolism and alternative splicing and have in common the presence of low complexity domains (LCD) that are prone to self-assemble and form aggregates. The mechanism of cytoplasmic protein aggregation remains elusive. Stress granules (SGs) that are micrometric RNA-protein assemblies located in the cytoplasm of cells exposed to environmental stress are suspected to play the role of seeds. The review sheds light on the recent experimental results that suggest a link between SGs and cytoplasmic protein aggregates but also propose other routes for the formation of these aggregates. Purpose of Review To analyze the potential relationship between cytoplasmic protein aggregates in neurons of affected subjects and stress granules. Recent Findings Liquid phase separation explains how protein and RNA could assemble in membraneless compartments, notably SGs. These results highlight the importance of RBPs with LCD in the SG assembly. Maturation of SGs and in particular the dense core is a potential source of insoluble protein aggregates. Summary Several lines of evidence linked stress granule dynamics to pathogenic protein aggregates. (i) Proteins that accumulate in cytoplasmic aggregates are also SG components. (ii) Neurons are specifically exposed to stress events due to their high metabolism and long lifespan. (iii) Diseases linked protein mutations affect the SG dynamics. (iv) SG dense core could be a breeding ground for protein aggregates. However, we should also keep in mind that SGs are not the only RNA-protein assembly in the cytoplasm; the RNA transport granules could also play a role in the formation of insoluble protein aggregates.