# Potential role of stress granules and myogranules in amyotrophic lateral sclerosis

## TL;DR

This review discusses how stress granules and myogranules, which involve the TDP-43 protein, may play a role in the development of amyotrophic lateral sclerosis.

## Contribution

The paper provides a focused review on the potential roles of stress granules and myogranules in ALS pathogenesis.

## Key findings

- TDP-43 aggregates in cytoplasm are common in ALS and may contribute to disease progression.
- Stress granules and myogranules are RNA-protein assemblies linked to TDP-43 and may influence ALS pathology.
- Current understanding of SG and MG formation and regulation is reviewed, along with research gaps.

## Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of upper and lower motor neurones, leading to muscle wasting, paralysis and respiratory failure. Pathological cytoplasmic aggregation of the RNA-binding protein transactive response DNA-binding protein 43 (TDP-43) protein occurs in neural tissues in ~97% of all ALS cases, and is also observed in skeletal muscle. Cytoplasmic aggregation of TDP-43 is believed to contribute to ALS pathogenesis; however, its precise mechanistic role/s continues to elude the field. This mini review explores the potential role and regulation of two TDP-43-associated RNA-protein assemblies, stress granules (SGs) and myogranules (MGs). We review the current understanding of SG and MG formation and their potential role in ALS-related neurodegeneration and muscle pathology. We also highlight limitations and strengths and suggest future directions for research.