Evidence map›Paper›PMID 33984771›Full record

ArticleBiochemical and biophysical research communications2021

Structural insight into transmissive mutant huntingtin species by correlative light and electron microscopy and cryo-electron tomography.

Xuyuan Kuang, Kyle Nunn, Jennifer Jiang, Paul Castellano, Uttara Hardikar, Arianna Horgan, Joyce Kong, Zhiqun Tan, Wei Dai

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemical and biophysical research communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 40% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Extracellular vesicle-based therapies for neurodegenerative diseases.NeuroImmune pharmacology and therapeutics · 2025
    Review
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Xuyuan KuangDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Kyle NunnDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Jennifer JiangDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Paul CastellanoDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Uttara HardikarDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Arianna HorganInstitute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Joyce KongInstitute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Zhiqun TanDepartment of Anatomy and Neurobiology, University of California Irvine School of Medicine, Irvine, CA, 29697, USA; Institute for Memory Impairment and Neurological Disorders, University of California-Irvine, Irvine, CA, 29697, USA. Electronic address: tanz@uci.edu.
Wei DaiDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA. Electronic address: wei.dai@rutgers.edu.
Rutgers, The State University of New Jersey · USUniversity of California, Irvine · US

Funding

Project 3: TRiC modulation of CNS pathogenesis in HD mouse modelsP01NS092525 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI THOMPSON, LESLIE MICHELS · 2016 to 2020
$6.3M
NINDS NIH HHS P01 NS092525
6 · The paper itself

Abstract

Aggregates of mutant huntingtin (mHTT) containing an expanded polyglutamine (polyQ) tract are hallmarks of Huntington's Disease (HD). Studies have shown that mHTT can spread between cells, leading to the propagation of misfolded protein pathology. However, the structure of transmissive mHTT species, and the molecular mechanisms underlying their transmission remain unknown. Using correlative light and electron microscopy (CLEM) and cryo-electron tomography (cryo-ET), we identified two types of aggregation-prone granules in conditioned medium from PC12 cells expressing a mHTT N-terminal fragment: densities enclosed by extracellular vesicles (EVs), and uncoated, amorphous meshworks of heterogeneous oligomers that co-localize with clusters of EVs. In vitro assays confirmed that liposomes induce condensation of polyQ oligomers into higher-order assemblies, resembling the uncoated meshworks observed in PC12 conditioned medium. Our findings provide novel insights into formation and architecture of transmissive mHTT proteins, and highlight the potential role of EVs as both carriers and modulators of transmissive mHTT proteins.

Indexed as

AnimalsCulture Media, ConditionedElectron Microscope TomographyHuntingtin ProteinLiposomesMicroscopyMicroscopy, ElectronMutationPC12 CellsProtein FoldingRatsCulture Media, ConditionedHuntingtin ProteinLiposomesCryo-electron tomographyExtracellular vesiclesMutant huntingtinProtein transmission

Identifiers

PMID33984771
PMCPMC8176346
OpenAlexW3161382540

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.