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38/100

✓ Peer-reviewed alzhub usefulness score 38 out of 100. Disease mechanisms

Topic: Brain proteins, microglia and lab models

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.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Riad, A., Lengyel-Zhand, Z., Zeng, C., Weng, C. C., Lee, V. M., Trojanowski, J. Q., et al. (2020). The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates. Molecular neurobiology. https://doi.org/10.1007/s12035-020-01988-1

Vancouver

Riad A, Lengyel-Zhand Z, Zeng C, Weng CC, Lee VM, Trojanowski JQ, et al. The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates. Molecular neurobiology. 2020. doi:10.1007/s12035-020-01988-1. PMID: 32572762.

BibTeX

@article{riad2020-32572762,
  author  = {Riad, A. and Lengyel-Zhand, Z. and Zeng, C. and Weng, C. C. and Lee, V. M. and Trojanowski, J. Q. and Mach, R. H.},
  title   = {{The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates}},
  journal = {Molecular neurobiology},
  year    = {2020},
  doi     = {10.1007/s12035-020-01988-1},
  pmid    = {32572762},
  url     = {https://doi.org/10.1007/s12035-020-01988-1}
}

Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.

Key findings

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).
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.
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.

Study details

Evidence strengthLow

How this study scored 38/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Molecular neurobiology)
Journal's citation record	— / 4	No journal record from OpenAlex — left out of this score
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	2 / 5	2020 — within 10 year(s) of the newest study here
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	— / 7	No citation count (not found in OpenAlex) — left out of this score
Citations per year	— / 5	No citation count or no year — left out of this score
Impact for its field and year	— / 6	No field-weighted citation impact (OpenAlex has none yet) — left out of this score
Cited by studies here	— / 6	Not yet checked against this library's citation graph — left out of this score
Still being cited	— / 4	No yearly citation counts — left out of this score
Senior author's track record	— / 4	Senior author's record not available — left out of this score
Institution's track record	— / 3	No institution listed in OpenAlex — left out of this score
Multi-centre collaboration	— / 3	Institutions not listed — left out of this score
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 32572762)
Free to read	0 / 2	Behind a paywall — scores zero
Points	22 / 58	Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100.
Total	38 / 100	—

What each of these 20 components measures, and what this score is not →

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