Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS?

Topic: Brain proteins, microglia and lab models

Stress granules (SGs) are RNA-containing cytoplasmic foci formed in response to stress exposure. Since their discovery in 1999, over 120 proteins have been described to be localized to these structures (in 154 publications). Most of these components are RNA binding proteins (RBPs) or are involved in RNA metabolism and translation.

@article{aulas2015-26557057,
  author  = {Aulas, A. and Vande Velde, C.},
  title   = {{Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS?}},
  journal = {Frontiers in cellular neuroscience},
  year    = {2015},
  doi     = {10.3389/fncel.2015.00423},
  pmid    = {26557057},
  url     = {https://doi.org/10.3389/fncel.2015.00423}
}

Key findings

• Since their discovery in 1999, over 120 proteins have been described to be localized to these structures (in 154 publications).
• Most of these components are RNA binding proteins (RBPs) or are involved in RNA metabolism and translation.
• SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
• In ALS and FTD, the majority of cases have no known etiology and exposure to external stress is frequently proposed as a contributor to either disease initiation or the rate of disease progression.

Why it matters

This paper discusses stress granules and their link to neurodegenerative diseases such as ALS and frontotemporal dementia, not Alzheimer's disease. It does not report any treatment, cure or prevention for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.3389/fncel.2015.00423
• PubMed: 26557057
• Original source →
• Free full text: Frontiers in Cellular Neuroscience →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 14.

• TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis Science · 2008-02-28 · usefulness score 64/100 · Disease mechanisms
• Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis Science (New York, N.Y.) · 2006-10-01 · usefulness score 62/100 · Lewy body dementia
• Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis Neuron · 2013-08-01 · usefulness score 58/100 · Lewy body dementia
• TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis Biochemical and biophysical research communications · 2006-10-30 · usefulness score 56/100 · Lewy body dementia
• TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration Human molecular genetics · 2010-04-15 · usefulness score 56/100 · Lewy body dementia
• Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs Nature neuroscience · 2012-09-30 · usefulness score 56/100 · Lewy body dementia
• Tar DNA binding protein-43 (TDP-43) associates with stress granules: analysis of cultured cells and pathological brain tissue PloS one · 2010-10-11 · usefulness score 55/100 · Lewy body dementia
• Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations Neuron · 2014-02-01 · usefulness score 55/100 · Lewy body dementia
• ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import The EMBO journal · 2010-07-06 · usefulness score 53/100 · Lewy body dementia
• The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease Brain research · 2012-01-21 · usefulness score 52/100 · Lewy body dementia
• Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function Cell · 2013-06-01 · usefulness score 52/100 · Lewy body dementia
• TDP-43 is recruited to stress granules in conditions of oxidative insult Journal of neurochemistry · 2009-09-16 · usefulness score 51/100 · Lewy body dementia

Later studies that cite this one

5 studies in the alzhub library list this one in their references.

• TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics Neuron · 2017-08-01 · usefulness score 58/100 · Caregiving
• TDP-43 proteinopathies: a new wave of neurodegenerative diseases Journal of neurology, neurosurgery, and psychiatry · 2020-11-11 · usefulness score 54/100 · Lewy body dementia
• Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis Frontiers in molecular neuroscience · 2019-02-14 · usefulness score 50/100 · Lewy body dementia
• Physiological functions and pathobiology of TDP-43 and FUS/TLS proteins Journal of neurochemistry · 2016-06-15 · usefulness score 49/100 · Lewy body dementia
• The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes Viruses · 2025-05-19 · usefulness score 39/100 · Brain tissue and pathology

Related studies in Brain tissue and pathology

• PARylation regulates stress granule dynamics, phase separation, and neurotoxicity of disease-related RNA-binding proteins Cell research · 2019-02-06 · usefulness score 49/100
• Neuroimmune signaling mediates astrocytic nucleocytoplasmic disruptions and stress granule formation associated with TDP-43 pathology Neurobiology of Disease · 2025-05-06 · usefulness score 39/100
• Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD Neuron · 2019-07-01 · usefulness score 52/100
• Understanding the role of TDP-43 and FUS/TLS in ALS and beyond Current opinion in neurobiology · 2011-08-02 · usefulness score 48/100
• FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis Journal of neurology, neurosurgery, and psychiatry · 2009-12-03 · usefulness score 49/100
• TDP-43 oxidation and PP1 crosstalk at RNA granule-mitochondria contact sites Nature Communications · 2026-06-05 · usefulness score 41/100

Also tagged “tdp-43”

1,150 studies in the library carry the topic tag “tdp-43”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.

• Microglial immunoreceptor tyrosine-based activation and inhibition motif signaling in neuroinflammation International journal of Alzheimer's disease · 2010-06-22 · usefulness score 41/100 · TREM2 and immune genetics
• Higher frequency of regulatory T cells in the elderly and increased suppressive activity in neurodegeneration Journal of neuroimmunology · 2007-06-19 · usefulness score 40/100 · Inflammation and the immune system
• Nerve growth factor increases mRNA levels for the prion protein and the beta-amyloid protein precursor in developing hamster brain Proceedings of the National Academy of Sciences of the United States of America · 1988-12-01 · usefulness score 43/100 · Down syndrome and Alzheimer's

Similar studies

• TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia 2010 · Lewy body dementia
• Amyloid-β, Tau Protein, α-Synuclein, TDP-43, and FUS in Mixed Pathology: And Intrinsic Disorder to Rule Them All 2026 · Brain tissue and pathology
• Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy 2019 · Clinical safety
• ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS 2018 · Disease mechanisms
• TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD 2018 · Lewy body dementia
• Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses 2025 · Brain tissue and pathology

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