Stress granules as potential biomarkers for neurodegenerative diseases

Stress pellets (SGs) are temporary organelles that form when cells experience stress, which serve as critical hubs for RNA metabolism and cellular survival. Consisting of RNA-binding proteins and nucleic acids, show SG’s liquid-like properties and are involved in processes such as mrna regulation and protein synthesis. However, the dysfunction of SGS is involved in various neurodegenerative diseases, including amyotrophe lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although their role in pathology is assumed, the exact mechanisms with which SGs interact with other cellular structures and contributions to disease progression, in particular through interactions with other organelles, is elusive. This knowledge gap has a need for in-depth research into SG dynamics and causes their cellular interactions.

Published in a review (DOI: 10,1093/Procel/PWAE057) Protein and cell On October 23, 2024, researchers from Beijing University Health Science Center will discuss how SGS interacts with different cellular organelles and how these interactions influence neurodegenerative disease issues. With the help of advanced techniques such as proximity labeling and biochemical fractionation, critical shared components between SGs and other cellular structures have been identified, including processing bodies, paraspecks and membranic entities such as lysosomes and the endoplasmic reticulum. These findings offer new insights into the interactions between SGs and other cellular organelles, and their collective roles in RNA metabolism and cellular reactions to stress.

One of the most important discoveries is the dynamic relationship between SGs and Promyelocytar leukemia (PML) Nuclear bodies, which plays a crucial role in the clearing of toxic intranuclear inclusions linked to neurodegenerative diseases. The assessment also sheds light on the role of annexine A11 in facilitating the interaction between SGs and lysosomes, which influences the transport and stability of RNA granules. Moreover, the assessment emphasizes the potential of SGs as biomarkers for early diagnosis and monitoring of ALS and FTD, which in the future indicates the promise of non-invasive diagnostic tools.

Dr. Peipei Zhang, the corresponding author of the assessment article, emphasizes the meaning of understanding SG dynamics: this review discusses how SGs coordinate with other organelles to regulate cellular stress reactions. Dys regulation of these interactions can stimulate neurodegeneration, with new goals for therapeutic intervention.

The findings discussed in this assessment article have a lot of promise to promote the development of targeted therapies for neurodegenerative diseases. By mapping the interactions between SGs and other cellular organelles, this review lays the basis for therapeutic interventions aimed at modulating these processes to delay disease progression. Moreover, the potential for SGs to serve as biomarkers for an early stage diagnosis can improve patient outcomes by making timely intervention possible. This review underlines the importance of further investigating cellular organelles to identify new strategies for combating neurodegenerative diseases, which may reform the future of disease management and patient care.