Evidence map›Paper›PMID 28612181›Full record

ArticleNeuromolecular medicine2017

Low-Density Lipoprotein Receptor-Related Protein-1 (LRP1) C4408R Mutant Promotes Amyloid Precursor Protein (APP) α-Cleavage in Vitro.

Huayan Hou, Ahsan Habib, Dan Zi, Kathy Tian, Jun Tian, Brian Giunta, Darrell Sawmiller, Jun Tan

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

Article in Neuromolecular medicine, 2017. 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
0.5field-weighted citation impact, top 35% 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, 5 citations in OpenAlex.

  1. Review
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  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

8 authors at 2 institutions in 2 countries.

Huayan HouRashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, FL, 33613, USA.
Ahsan HabibRashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, FL, 33613, USA.
Dan ZiRashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, FL, 33613, USA.
Kathy TianRashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, FL, 33613, USA.
Jun TianRashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, FL, 33613, USA.
Brian GiuntaNeuroimmunology Laboratory, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, 33613, USA.
Darrell SawmillerRashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, FL, 33613, USA. dsawmill@health.usf.edu.ORCID http://orcid.org/0000-0003-3599-6859
Jun TanRashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, FL, 33613, USA.
University of South Florida · USGuiyang Medical University · CN

Funding

LISPRO, an ionic cocrystal of lithium, as a potential novel treatment for Alzheimer's diseaseR01AG050253 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI TAN, JUN · 2016 to 2019
$1.5M
Implication of HUCBC: a novel therapeutic strategy for Alzheimer's diseaseR01AG032432 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI TAN, JUN · 2009 to 2013
$1.4M
Flavonoid-diosmin modulation of Abeta and tau pathologies through GSK-3 signalingR01AT007411 · NCCIH · UNIVERSITY OF SOUTH FLORIDA · PI TAN, JUN · 2014 to 2015
$663k
Identification of novel APP-specific alpha secretase in human umbilical cord blood seraR21AG055116 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI TAN, JUN · 2017 to 2018
$411k
NCCIH NIH HHS R01 AT007411NIA NIH HHS R01 AG032432NIA NIH HHS R01 AG050253NIA NIH HHS R21 AG055116
6 · The paper itself

Abstract

Previous studies have demonstrated that the low-density lipoprotein receptor-related protein-1 (LRP1) plays conflicting roles in Alzheimer's disease (AD) pathogenesis, clearing β-amyloid (Aβ) from the brain while also enhancing APP endocytosis and resultant amyloidogenic processing. We have recently discovered that co-expression of mutant LRP1 C-terminal domain (LRP1-CT C4408R) with Swedish mutant amyloid precursor protein (APPswe) in Chinese hamster ovary (CHO) cells decreases Aβ production, while also increasing sAPPα and APP α-C-terminal fragment (α-CTF), compared with CHO cells expressing APPswe alone. Surprisingly, the location of this mutation on LRP1 corresponded with the α-secretase cleavage site of APP. Further experimentation confirmed that in CHO cells expressing APPswe or wild-type APP (APPwt), co-expression of LRP1-CT C4408R decreases Aβ and increases sAPPα and α-CTF compared with co-expression of wild-type LRP1-CT. In addition, LRP1-CT C4408R enhanced the unglycosylated form of LRP1-CT and reduced APP endocytosis as determined by flow cytometry. This finding identifies a point mutation in LRP1 which slows LRP1-CT-mediated APP endocytosis and amyloidogenic processing, while enhancing APP α-secretase cleavage, thus demonstrating a potential novel target for slowing AD pathogenesis.

Indexed as

Mutation, MissensePoint MutationAlzheimer DiseaseAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsBase SequenceCHO CellsCricetinaeCricetulusEndocytosisHumansLow Density Lipoprotein Receptor-Related Protein-1Protein DomainsRecombinant ProteinsAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesLow Density Lipoprotein Receptor-Related Protein-1LRP1 protein, humanRecombinant ProteinsAlzheimer’s disease (AD)Amyloid precursor protein (APP)Low-density lipoprotein receptor-related protein-1 (LRP1)Secreted amyloid precursor protein-alpha (sAPPα)Swedish mutant APP (APPswe)β-Amyloid (Aβ)

Identifiers

PMID28612181
PMCPMC5693694
OpenAlexW2625902129

What OpenQuestion holds

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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.