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Cited by 11Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchHeat shock proteins research

Decreases in valosin-containing protein result in increased levels of tau phosphorylated at Ser262/356

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Dolan, Philip J., Jin, Youngnam N., Hwang, Woong, Johnson, Gail V.W.·2011·FEBS Letters
DOI 10.1016/j.febslet.2011.09.032PMC PMC3209510
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Abstract

VCP/p97 is a multifunctional AAA+-ATPase involved in vesicle fusion, proteasomal degradation, and autophagy. Reported dysfunctions of these processes in Alzheimer disease (AD), along with the linkage of VCP/p97 to inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD) led us to examine the possible linkage of VCP to the AD-relevant protein, tau. VCP levels were reduced in AD brains, but not in the cerebral cortex of an AD mouse model, suggesting that VCP reduction occurs upstream of tau pathology. Genetic reduction of VCP in a primary neuronal model led to increases in the levels of tau phosphorylated at Ser(262/356), indicating that VCP may be involved in regulating post-translational processing of tau in AD, demonstrating a possible functional linkage between tau and VCP.

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  • Aggregated tau or tau phosphorylated at Ser262/356 is degraded by the autophagy-lysosome system.

    “The majority of tau species (including tau lacking phosphorylation at Ser262/356) are degraded by the proteasome [20], while aggregated tau or tau phosphorylated at Ser262/356 is degraded by the autophagy-lysosome system [79–84].”

    From Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity (2016) · cites this paper as [81]

    The Discussion states that tau phosphorylated at KXGS motifs is degraded by autophagy rather than the proteasome, and §3.4 reports increased soluble Ser262/356-phosphorylated tau after autophagy inhibition. These passages support the phosphorylated-tau part of the claim, but our copy does not establish that aggregated tau is degraded by the autophagy-lysosome system; the study reports no change in insoluble tau after VCP knockdown. (LLM, conf=0.87)

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Research works printed but not linked: 27

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Cited by

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Authors
Dolan, P. J., Jin, Y. N., Hwang, W., & Johnson, G. V. W.
Affiliations
  • University of Alabama at Birmingham (US)
  • University of Rochester (US)
  • University of Rochester Medicine (US)
Corresponding author
Johnson, Gail V.W.
ORCID
Venue
FEBS Letters
Publisher
Wiley
Published
2011-10-04
Volume
585
Issue
21
Pages
3424-3429
ISSN
0014-5793 (ISSN-L)
DOI
10.1016/j.febslet.2011.09.032
PMC
PMC3209510
OpenAlex
W1970252802
Cited by
11
References
2
Citations by year
2026: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 1
FWCI
0.41
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1428 d)
Locations
  • FEBS Letters (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (NS051279, NS041744)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
VCP, VCP/p97, tau phosphorylation, Alzheimer's disease, AAA+ ATPase, neuron models, protein quality control
MeSH terms
Valosin Containing Protein, Adenine, Adenosine Triphosphatases, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Autophagy, Cerebral Cortex, Female, Humans, Male, Middle Aged, Neurons, Phosphoproteins, Phosphorylation, Serine, Solubility, tau Proteins, Cell Cycle Proteins, Mice, Rats, Gene Knockdown Techniques, HEK293 Cells

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