CoChat
Sign Up
Cited by 31Genetic Neurodegenerative DiseasesExtracellular vesicles in diseaseLysosomal Storage Disorders Research

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

DNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease

Open access
Joshi, Bhagyashree S., Youssef, Sameh A., Bron, Reinier, de Bruin, Alain, Kampinga, Harm H., Zuhorn, Inge S.·2021·iScience
DOI 10.1016/j.isci.2021.103282PMC PMC8564107
Open this paper in CoChat — free accountOpen PDF

Abstract

Huntington disease (HD) is a devastating neurodegenerative disorder characterized by aggregation of huntingtin (HTT) protein containing expanded polyglutamine (polyQ) tracts. DNAJB6, a member of the DNAJ chaperone family, was reported to efficiently inhibit polyQ aggregation in vitro , in cell models, and in vivo in flies, xenopus, and mice. For the delivery of exogenous DNAJB6 to the brain, the DNAJB6 needs to be protected against (enzymatic) degradation and show good penetration into brain tissue. Here, we tested the potential of small extracellular vesicles (sEVs) derived from neural stem cells (NSCs) for delivery of DNAJB6 as anti-amyloidogenic cargo. Administration of sEVs isolated from DNAJB6-overexpressing cells to cells expressing expanded polyQ tracts suppressed HTT aggregation. Furthermore, intrathecal injection of DNAJB6-enriched sEVs into R6/2 transgenic HD mice significantly reduced mutant HTT aggregation in the brain. Taken together, our data suggest that sEV-mediated molecular chaperone delivery may hold potential to delay disease onset in HD.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.isci.2021.103282

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 43

  1. Alpaugh, 2017, Disease-modifying effects of ganglioside GM1 in Huntington's disease models, EMBO Mol. Med., 9, 1537, 10.15252/emmm.201707763 · DOI
  2. Balch, 2008, Adapting proteostasis for disease intervention, Science (New York, NY), 319, 916, 10.1126/science.1141448 · DOI · Paper page
  3. Balchin, 2016, In vivo aspects of protein folding and quality control, Science (New York, NY), 353, aac4354, 10.1126/science.aac4354 · DOI
  4. Bason, 2019, Astrocytic expression of the chaperone DNAJB6 results in non-cell autonomous protection in Huntington's disease, Neurobiol. Dis., 124, 108, 10.1016/j.nbd.2018.10.017 · DOI
  5. Bobrie, 2012, Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation, J. Extracell. Vesicles, 1
  6. Chai, 1999, Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease, J. Neurosci., 19, 10338, 10.1523/JNEUROSCI.19-23-10338.1999 · DOI
  7. Davies, 1997, Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation, Cell, 90, 537, 10.1016/S0092-8674(00)80513-9 · DOI
  8. Dedeoglu, 2003, Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice, J. Neurochem., 85, 1359, 10.1046/j.1471-4159.2003.01706.x · DOI · Paper page
  9. Ferrante, 2009, Mouse models of Huntington's disease and methodological considerations for therapeutic trials, Biochim. Biophys. Acta, 1792, 506, 10.1016/j.bbadis.2009.04.001 · DOI
  10. Hageman, 2010, A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation, Mol. Cell, 37, 355, 10.1016/j.molcel.2010.01.001 · DOI
  11. Hoshino, 2015, Tumour exosome integrins determine organotropic metastasis, Nature, 527, 329, 10.1038/nature15756 · DOI · Paper page
  12. Howarth, 2007, Hsp40 molecules that target to the ubiquitin-proteasome system decrease inclusion formation in models of polyglutamine disease, Mol. Ther., 15, 1100, 10.1038/sj.mt.6300163 · DOI
  13. Jahn, 2005, The Yin and Yang of protein folding, Febs j, 272, 5962, 10.1111/j.1742-4658.2005.05021.x · DOI
  14. Kakkar, 2016, The S/T-Rich motif in the DNAJB6 chaperone delays polyglutamine aggregation and the onset of disease in a mouse model, Mol. Cell, 62, 272, 10.1016/j.molcel.2016.03.017 · DOI
  15. Kuiper, 2017, Chaperones in polyglutamine aggregation: beyond the Q-stretch, Front Neurosci., 11, 145, 10.3389/fnins.2017.00145 · DOI
  16. Labbadia, 2012, Suppression of protein aggregation by chaperone modification of high molecular weight complexes, Brain, 135, 1180, 10.1093/brain/aws022 · DOI
  17. Lee, 2016, Cellular engineering with membrane fusogenic liposomes to produce functionalized extracellular vesicles, ACS Appl. Mater. Inter., 8, 6790, 10.1021/acsami.6b01315 · DOI
  18. Lee, 2017, Exosome-based delivery of miR-124 in a Huntington's disease model, J. Move. Disord., 10, 45
  19. Mangiarini, 1996, Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice, Cell, 87, 493, 10.1016/S0092-8674(00)81369-0 · DOI · Paper page
  20. Mansson, 2014, Interaction of the molecular chaperone DNAJB6 with growing amyloid-beta 42 (Abeta42) aggregates leads to sub-stoichiometric inhibition of amyloid formation, J. Biol. Chem., 289, 31066, 10.1074/jbc.M114.595124 · DOI
  21. Mansson, 2018, Conserved S/T residues of the human chaperone DNAJB6 are required for effective inhibition of Abeta42 amyloid fibril formation, Biochemistry, 57, 4891, 10.1021/acs.biochem.8b00353 · DOI
  22. Mathieu, 2019, Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication, Nat. Cell Biol., 21, 9, 10.1038/s41556-018-0250-9 · DOI
  23. Meng, 2016, Emerging roles and underlying molecular mechanisms of DNAJB6 in cancer, Oncotarget, 7, 53984, 10.18632/oncotarget.9803 · DOI
  24. Muller-Taubenberger, 2006, Monomeric red fluorescent protein variants used for imaging studies in different species, Eur. J. Cell Biol., 85, 1119, 10.1016/j.ejcb.2006.05.006 · DOI
  25. Nakase, 2015, Combined treatment with a pH-sensitive fusogenic peptide and cationic lipids achieves enhanced cytosolic delivery of exosomes, Sci. Rep., 5, 10112, 10.1038/srep10112 · DOI
  26. Orr, 2007, Trinucleotide repeat disorders, Annu. Rev. Neurosci., 30, 575, 10.1146/annurev.neuro.29.051605.113042 · DOI
  27. Ramirez, 2018, Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers, Fluids Barriers CNS, 15, 19, 10.1186/s12987-018-0104-7 · DOI · Paper page
  28. Ross, 2011, Huntington's disease: from molecular pathogenesis to clinical treatment, Lancet Neurol., 10, 83, 10.1016/S1474-4422(10)70245-3 · DOI
  29. Schneider, 2013, Exosomes: vesicular carriers for intercellular communication in neurodegenerative disorders, Cell Tissue Res., 352, 33, 10.1007/s00441-012-1428-2 · DOI
  30. Narain, 1999, A molecular investigation of true dominance in Huntington’s disease, J Med Genet, 36, 739, 10.1136/jmg.36.10.739 · DOI
  31. O'Donovan, 1993, A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes, Cell, 72, 971, 10.1016/0092-8674(93)90585-E · DOI · Paper page
  32. Shen, 2011, Protein targeting to exosomes/microvesicles by plasma membrane anchors, J. Biol. Chem., 286, 14383, 10.1074/jbc.M110.208660 · DOI
  33. Skotland, 2017, Lipids in exosomes: current knowledge and the way forward, Prog. Lipid Res., 66, 30, 10.1016/j.plipres.2017.03.001 · DOI · Paper page
  34. Sterzenbach, 2017, Engineered exosomes as vehicles for biologically active proteins, Mol. Ther., 25, 1269, 10.1016/j.ymthe.2017.03.030 · DOI
  35. Takeuchi, 2015, Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level, Proc. Natl. Acad. Sci. U S A, 112, E2497, 10.1073/pnas.1412651112 · DOI
  36. Thery, 2002, Exosomes: composition, biogenesis and function, Nat. Rev. Immunol., 2, 569, 10.1038/nri855 · DOI
  37. Thiruvalluvan, 2020, DNAJB6, a key factor in neuronal sensitivity to amyloidogenesis, Mol. Cell, 78, 346, 10.1016/j.molcel.2020.02.022 · DOI
  38. Tkach, 2016, Communication by extracellular vesicles: where we are and where we need to go, Cell, 164, 1226, 10.1016/j.cell.2016.01.043 · DOI · Paper page
  39. Valenza, 2015, Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice, EMBO Mol. Med., 7, 1547, 10.15252/emmm.201505413 · DOI · Paper page
  40. Wanker, 1999, Membrane filter assay for detection of amyloid-like polyglutamine-containing protein aggregates, Methods Enzymol., 309, 375, 10.1016/S0076-6879(99)09026-6 · DOI
  41. Warrick, 1999, Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70, Nat. Genet., 23, 425, 10.1038/70532 · DOI
  42. Yang, 2013, The cis-acting signals that target proteins to exosomes and microvesicles, Biochem. Soc. Trans., 41, 277, 10.1042/BST20120275 · DOI
  43. Zomer, 2015, In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior, Cell, 161, 1046, 10.1016/j.cell.2015.04.042 · DOI

Cited by

Sorted by citations

Metadata

Authors
Joshi, B. S., Youssef, S. A., Bron, R., de Bruin, A., Kampinga, H. H., & Zuhorn, I. S.
Affiliations
University Medical Center Groningen (NL)
Corresponding author
Zuhorn, Inge S.
ORCID
Venue
iScience
Publisher
Elsevier BV
Published
2021-11
Volume
24
Issue
11
Pages
103282
ISSN
2589-0042 (ISSN-L)
DOI
10.1016/j.isci.2021.103282
PMC
PMC8564107
OpenAlex
W3205397583
Cited by
31
References
4
Citations by year
2026: 2 · 2025: 7 · 2024: 8 · 2023: 4 · 2022: 10
FWCI
2.65
Type
journal article
Language
en
Open access
Licence
Locations
  • iScience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
  • European Commission
  • Ministerie van Economische Zaken
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
  • Dutch Research Council Domain Science
  • Stichting De Cock - Hadders
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
Keywords
Huntington's disease, DNAJB6, small extracellular vesicles, neural stem cells, polyglutamine aggregation, huntingtin aggregation, DnaJ chaperone, intrathecal drug delivery, R6/2 transgenic mice, neurodegeneration

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review