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Cited by 129Alzheimer's disease research and treatmentsRNA Research and SplicingAmyotrophic Lateral Sclerosis Research

Pathological stress granules in Alzheimer’s disease

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Ash, Peter E.A., Vanderweyde, Tara E., Youmans, Katherine L., Apicco, Daniel J., Wolozin, Benjamin·2014·Brain Research
DOI 10.1016/j.brainres.2014.05.052PMC PMC4256948
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Abstract

A feature of neurodegenerative disease is the accumulation of insoluble protein aggregates in the brain. In some conditions, including Amyotrophic Lateral Sclerosis and Frontotemporal lobar degeneration, the primary aggregating entities are RNA binding proteins. Through regulated prion-like assembly, RNA binding proteins serve many functions in RNA metabolism that are essential for the healthy maintenance of cells of the central nervous system. Those RNA binding proteins that are the core nucleating factors of stress granules (SGs), including TIA-1, TIAR, TTP and G3BP1, are also found in the pathological lesions of other neurological conditions, such as Alzheimer's disease, where the hallmark aggregating protein is not an RNA binding protein. This discovery suggests that the regulated cellular pathway, which utilizes assembly of RNA binding proteins to package and silence mRNAs during stress, may be integral in the aberrant pathological protein aggregation that occurs in numerous neurodegenerative conditions.

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  • Cell body MAPT pathology colocalizes with markers of the translational stress response, such as stress granule proteins HNRNPA2B1, TIA1, EIF3n and PABP, and also neuronal death (cleaved caspase 3 and loss of NeuN positive cells).

    “The cell body MAPT pathology is particularly important because this pathology colocalizes with markers of the translational stress response, such as stress granule proteins HNRNPA2B1, TIA1, EIF3n and PABP, and also neuronal death (as shown by cleaved caspase 3 and loss of NeuN positive cells) (Ash et al., 2014; Apicco et al., 2018; Maziuk et al., 2018; Apicco et al., 2019; Jiang et al., 2019, 2021”

    From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Ash et al., 2014

    The 'SGs in Neurodegenerative disease' section reports that TIA-1 colocalizes with pathological tau in affected neurons, supporting that part of the claim. It does not report colocalization with HNRNPA2B1, EIF3n or PABP, or demonstrate neuronal death by cleaved caspase 3 or loss of NeuN-positive cells. The same section cautions that tau pathology in a neuron is not necessarily correlated with that neuron's demise. No page numbers are available in our copy. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Ash, P. E. A., Vanderweyde, T. E., Youmans, K. L., Apicco, D. J., & Wolozin, B.
Affiliations
Boston University (US)
Corresponding author
Wolozin, Benjamin
ORCID
Venue
Brain Research
Publisher
Elsevier BV
Published
2014-10
Volume
1584
Pages
52-58
ISSN
0006-8993 (ISSN-L)
DOI
10.1016/j.brainres.2014.05.052
PMC
PMC4256948
OpenAlex
W2004369408
Cited by
129
References
3
Citations by year
2026: 6 · 2025: 12 · 2024: 14 · 2023: 12 · 2022: 15 · 2021: 13 · 2020: 10 · 2019: 13 · 2018: 7 · 2017: 11 · 2016: 7 · 2015: 7 · 2014: 2
FWCI
6.00
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01AG050471)
  • National Institute of General Medical Sciences (T32GM008541)
  • National Institute of Neurological Disorders and Stroke (R01NS089544, R21NS066108, R21NS073679)
  • National Institute of Environmental Health Sciences (R01ES020395)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
stress granules, Alzheimer's disease, RNA-binding proteins, protein aggregation, TIA-1, TIAR, TTP, G3BP1, mRNA silencing, neurodegenerative diseases, amyotrophic lateral sclerosis, frontotemporal lobar degeneration
MeSH terms
RNA Recognition Motif Proteins, T-Cell Intracellular Antigen-1, Poly-ADP-Ribose Binding Proteins, Alzheimer Disease, Animals, Brain, Carrier Proteins, Cytoplasmic Granules, DNA Helicases, DNA-Binding Proteins, Humans, Stress, Physiological, Signal Transduction, RNA-Binding Proteins, RNA Helicases, Poly(A)-Binding Proteins, Mice, Tristetraprolin, Protein Aggregation, Pathological

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