Evidence map›Paper›PMID 33677647›Full record

ArticleActa neuropathologica2021

Patterns of neuronal Rhes as a novel hallmark of tauopathies.

Alexander J Ehrenberg, Kun Leng, Kaitlyn N Letourneau, Israel Hernandez, Caroline Lew, William W Seeley, Salvatore Spina, Bruce Miller, Helmut Heinsen, Martin Kampmann and 2 more

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

Article in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 25% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
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  4. Article
  5. Review
  6. Article
  7. Deletion of SUMO1 attenuates behavioral and anatomical deficits by regulating autophagic activities in Huntington disease.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  8. Article
  9. 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

12 authors at 4 institutions in 2 countries.

Alexander J EhrenbergMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, 675 Nelson Rising Lane, Box 1207, San Francisco, 94158, CA, USA.
Kun LengInstitute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, USA.
Kaitlyn N LetourneauDepartment of Integrative Biology, University of California, Berkeley, Berkeley, USA.
Israel HernandezNeuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, USA.
Caroline LewMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, 675 Nelson Rising Lane, Box 1207, San Francisco, 94158, CA, USA.
William W SeeleyMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, 675 Nelson Rising Lane, Box 1207, San Francisco, 94158, CA, USA.
Salvatore SpinaMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, 675 Nelson Rising Lane, Box 1207, San Francisco, 94158, CA, USA.
Bruce MillerMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, 675 Nelson Rising Lane, Box 1207, San Francisco, 94158, CA, USA.
Helmut HeinsenBiomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, USA.
Martin KampmannInstitute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, USA.
Kenneth S KosikNeuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, USA.
Lea T GrinbergMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, 675 Nelson Rising Lane, Box 1207, San Francisco, 94158, CA, USA. lea.grinberg@ucsf.edu.ORCID http://orcid.org/0000-0002-6809-0618
University of California, San Francisco · USUniversity of California, Santa Barbara · USUniversidade de São Paulo · BRUniversity of California, Berkeley · US

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Gil Dan Rabinovici · 2019 to 2026
$36.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
Project 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2016 to 2020
$10.8M
Clinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSPR01AG060477 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lea Tenenholz Grinberg, Thomas C Neylan · 2019 to 2026
$8.2M
Systematic elucidation of endosomal trafficking as a therapeutic opportunity in AD using CRISPR-based functional genomicsR01AG062359 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAMPMANN, MARTIN · 2018 to 2022
$3.2M
The complex interaction between Alzheimer drivers and agingRF1AG062479 · NIA · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI KOSIK, KENNETH STEPHEN · 2020 to 2020
$2.6M
Neuropathological changes underlying clinical heterogeneity in Alzheimer diseaseK24AG053435 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ · 2016 to 2025
$1.8M
Neuropathological basis of brain network dysfunctionK08AG052648 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SPINA, SALVATORE · 2016 to 2020
$852k
Uncovering mechanisms of selective vulnerability by CRISPR-based genetic screensR56AG057528 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ, KAMPMANN, MARTIN · 2018 to 2018
$769k
Elucidating cellular pathways controlling the reactive state of astrocytes in Alzheimer’s DiseaseF30AG066418 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LENG, KUN · 2019 to 2023
$155k
NIA NIH HHS F30 AG066418NIA NIH HHS F30AG066418NIA NIH HHS K08 AG052648NIA NIH HHS K08AG052648NIA NIH HHS K24 AG053435NIA NIH HHS K24AG053435NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG062422NIA NIH HHS R01 AG060477NIA NIH HHS R01 AG062359NIA NIH HHS R01AG062359NIA NIH HHS R56 AG057528NIA NIH HHS R56AG057528NIGMS NIH HHS T32 GM007618NINDS NIH HHS U54 NS100717NINDS NIH HHS U54NS100717
6 · The paper itself

Abstract

The farnesyltransferase inhibitor, Lonafarnib, reduces tau inclusions and associated atrophy in familial tauopathy models through activation of autophagy, mediated by the inhibition of farnesylation of the Ras GTPase, Rhes. While hinting at a role of Rhes in tau aggregation, it is unclear how translatable these results are for sporadic forms of tauopathy. We examined histological slides of allocortex and neocortex from multiple postmortem cases in five different tauopathies, FTLD-TDP, and healthy controls using immunofluorescence for Rhes, several tau post-translational modifications, and phospho-TDP-43. Single nucleus RNA data suggest that Rhes is found in all cortical neuron subpopulations but not in glia. Histologic investigation showed that nearly all neurons in control brains display a pattern of diffuse cytoplasmic Rhes positivity. However, in the presence of abnormal tau, but not abnormal TDP-43, the patterns of neuronal cytoplasmic Rhes tend to present as either punctiform or entirely absent. This observation reinforces the relevance of findings that link Rhes changes and tau pathology from the in vivo and in vitro models of tauopathy. The results here support a potential clinical application of Lonafarnib to tauopathies.

Indexed as

AgedAged, 80 and overFemaleFrontotemporal DementiaGTP-Binding ProteinsHumansMaleNeuronsTauopathiesGTP-Binding ProteinsRASD2 protein, humanAlzheimer's diseaseAutopsyFarnesyltransferaseHumanNeuropathologyTauopathies

Identifiers

PMID33677647
PMCPMC8418783
OpenAlexW3133676919

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.