Evidence map›Paper›PMID 32572762›Full record

ArticleMolecular neurobiology2020

The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates.

Aladdin Riad, Zsofia Lengyel-Zhand, Chenbo Zeng, Chi-Chang Weng, Virginia M-Y Lee, John Q Trojanowski, Robert H Mach

Open access · greenAbstract read
In one paragraph

Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 5% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021
    Trial
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Asymmetric Dynamics Between the Protomers of the σ2 Receptor Homodimer.Journal of chemical information and modeling · 2025
    Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Nrf2/Bach1 signaling axis: A promising multifaceted therapeutic strategy for Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  17. Article
  18. Article
  19. 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

7 authors at 2 institutions in 1 country.

Aladdin RiadDepartment of Radiology, University of Pennsylvania, Vagelos Laboratories, 1012, 231 S. 34th Street, Philadelphia, PA, 19104-6323, USA.
Zsofia Lengyel-ZhandDepartment of Radiology, University of Pennsylvania, Vagelos Laboratories, 1012, 231 S. 34th Street, Philadelphia, PA, 19104-6323, USA.
Chenbo ZengDepartment of Radiology, University of Pennsylvania, Vagelos Laboratories, 1012, 231 S. 34th Street, Philadelphia, PA, 19104-6323, USA.
Chi-Chang WengDepartment of Radiology, University of Pennsylvania, Vagelos Laboratories, 1012, 231 S. 34th Street, Philadelphia, PA, 19104-6323, USA.
Virginia M-Y LeeCenter for Neurodegenerative Disease Research, Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John Q TrojanowskiCenter for Neurodegenerative Disease Research, Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Robert H MachDepartment of Radiology, University of Pennsylvania, Vagelos Laboratories, 1012, 231 S. 34th Street, Philadelphia, PA, 19104-6323, USA. rmach@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-7645-2869
University of Pennsylvania · USInstitute for Neurodegenerative Disorders · US

Funding

T32 Translational Addiction Research Fellowship ProgramT32DA028874 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI Julie A Blendy, Anna Rose Childress · 2010 to 2026
$5.0M
Michael J. Fox Foundation for Parkinson's Research Ref: 14638.01NIDA NIH HHS 2T32DA028874-08NIDA NIH HHS T32 DA028874
6 · The paper itself

Abstract

Our lab has recently shown that the Sigma-2 Receptor/Transmembrane Protein 97 (TMEM97) and Progesterone Receptor Membrane Component 1 (PGRMC1) form a complex with the Low Density Lipoprotein Receptor (LDLR), and this intact complex is required for efficient uptake of lipoproteins such as LDL and apolipoprotein E (apoE). These receptors are expressed in the nervous system where they have implications in neurodegenerative diseases such as Alzheimer's disease (AD), where apoE is involved in neuronal uptake and accumulation of Aβ42, eventually cascading into neurodegeneration, synaptic dysfunction, and ultimately, dementia. We hypothesize that the intact Sigma-2 receptor complex-TMEM97, PGRMC1, and LDLR-is necessary for internalization of apoE and Aβ42 monomers (mAβ42) and oligomers (oAβ42), and the disruption of the receptor complex inhibits uptake. The results of this study suggest that the intact Sigma-2 receptor complex is a binding site for mAβ42 and oAβ42, in the presence or absence of apoE2, apoE3, and apoE4. The loss or pharmacological inhibition of one or both of these proteins results in the disruption of the complex leading to decreased uptake of mAβ42 and oAβ42 and apoE in primary neurons. The TMEM97, PGRMC1, and LDLR complex is a pathway for the cellular uptake of Aβ42 via apoE dependent and independent mechanisms. This study suggests that the complex may potentially be a novel pharmacological target to decrease neuronal Aβ42 internalization and accumulation, which may represent a new strategy for inhibiting the rate of neurotoxicity, neurodegeneration, and progression of AD.

Indexed as

Protein AggregatesAdultAmyloid beta-PeptidesAnimalsApolipoproteins ECell LineCells, CulturedCerebral CortexHumansMembrane ProteinsNeuronsPeptide FragmentsRatsReceptors, LDLReceptors, ProgesteroneAmyloid beta-Peptidesamyloid beta-protein (1-42)Apolipoproteins EMembrane ProteinsPeptide FragmentsPGRMC1 protein, humanProtein AggregatesReceptors, LDLReceptors, ProgesteroneTMEM97 protein, humanAlzheimer’s diseaseAmyloid betaApolipoproteinsNeuronsSigma 2 receptor

Identifiers

PMID32572762
PMCPMC7415709
OpenAlexW3036273457

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.