Evidence map›Paper›PMID 35507892›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Maximillian A Rogers, Catherine C Y Chang, Robert A Maue, Elaina M Melton, Andrew A Peden, William S Garver, Junghoon Lee, Peter Schroen, Mitchell Huang, Ta-Yuan Chang

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Sterol O-Acyltransferase 1 (International journal of molecular sciences · 2024
    Article
  11. Article
  12. Review
  13. Article
  14. Role of macrophage scavenger receptor 1 in the progression of dyslipidemia in acne vulgaris patients.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Profile of Ta-Yuan Chang.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  20. 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

10 authors at 3 institutions in 2 countries.

Maximillian A RogersDepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
Catherine C Y ChangDepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
Robert A MaueDepartment of Biology, Dartmouth College, Hanover, NH 03755.
Elaina M MeltonDepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
Andrew A PedenDepartment of Biomedical Science, Centre for Membrane Interactions and Dynamics, University of Sheffield, Sheffield S10 2TN, United Kingdom.ORCID 0000-0003-0144-7712
William S GarverDepartment of Chemistry & Chemical Biology, University of New Mexico, Albuquerque, NM 87131.
Junghoon LeeDepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
Peter SchroenDepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
Mitchell HuangDepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
Ta-Yuan ChangDepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.ORCID 0000-0002-3249-0468
Dartmouth College · USUniversity of New Mexico · USUniversity of Sheffield · GB

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3M
Understanding the role of RNA-binding protein mutations in cancerP20GM113132 · NIGMS · DARTMOUTH COLLEGE · PI MIERKE, DALE F · 2016 to 2025
$25.9M
Alleviating lysosomal lipid defects in ADRD by blocking cholesterol storageR01AG063544 · NIA · DARTMOUTH COLLEGE · PI CHANG, TA YUAN · 2018 to 2021
$2.3M
NCI NIH HHS P30 CA023108NIA NIH HHS R01 AG063544NIGMS NIH HHS P20 GM113132
6 · The paper itself

Abstract

Multiple membrane organelles require cholesterol for proper function within cells. The Niemann-Pick type C (NPC) proteins export cholesterol from endosomes to other membrane compartments, including the endoplasmic reticulum (ER), plasma membrane (PM), trans-Golgi network (TGN), and mitochondria, to meet their cholesterol requirements. Defects in NPC cause malfunctions in multiple membrane organelles and lead to an incurable neurological disorder. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), a resident enzyme in the ER, converts cholesterol to cholesteryl esters for storage. In mutant NPC cells, cholesterol storage still occurs in an NPC-independent manner. Here we report the interesting finding that in a mutant Npc1 mouse (Npc1nmf), Acat1 gene (Soat1) knockout delayed the onset of weight loss, motor impairment, and Purkinje neuron death. It also improved hepatosplenic pathology and prolonged lifespan by 34%. In mutant NPC1 fibroblasts, ACAT1 blockade (A1B) increased cholesterol content associated with TGN-rich membranes and mitochondria, while decreased cholesterol content associated with late endosomes. A1B also restored proper localization of syntaxin 6 and golgin 97 (key proteins in membrane trafficking at TGN) and improved the levels of cathepsin D (a key protease in lysosome and requires Golgi/endosome transport for maturation) and ABCA1 (a key protein controlling cholesterol release at PM). This work supports the hypothesis that diverting cholesterol from storage can benefit multiple diseases that involve cholesterol deficiencies in cell membranes.

Indexed as

LongevityNiemann-Pick Disease, Type CAcetyl-CoA C-AcetyltransferaseAlzheimer DiseaseAnimalsCholesterolCholesterol EstersDisease Models, AnimalEndosomesMiceNiemann-Pick C1 ProteinSterol O-AcyltransferaseAcat1 protein, mouseAcetyl-CoA C-AcetyltransferaseCholesterolCholesterol EstersNiemann-Pick C1 ProteinNpc1 protein, mouseSterol O-Acyltransferasesterol O-acyltransferase 1acyl-coenzyme A:cholesterol acyltransferasecholesterol esterificationNiemann-Pick disease type C

Identifiers

PMID35507892
PMCPMC9170141
OpenAlexW4228997845

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.