Evidence map›Paper›PMID 29871524›Full record

ArticleCell transplantation2018

Human Cord Blood Serum-Derived APP α-Secretase Cleavage Activity is Mediated by C1 Complement.

Ahsan Habib, Darrell Sawmiller, Huayan Hou, Manasa Kanithi, Jun Tian, Jin Zeng, Dan Zi, Zhi-Xu He, Paul R Sanberg, Jun Tan

Open access · goldAbstract read
In one paragraph

Article in Cell transplantation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. As a Potential Therapeutic Target, C1q Induces Synapse Loss Via Inflammasome-activating Apoptotic and Mitochondria Impairment Mechanisms in Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023
    Review
  3. 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.

Ahsan Habib1 Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Darrell Sawmiller1 Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Huayan Hou1 Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Manasa Kanithi1 Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Jun Tian1 Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Jin Zeng1 Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Dan Zi2 Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center & Sino-US Joint Laboratory for Medical Sciences, Laboratory Animal Center, Guizhou Medical University Guiyang, China.
Zhi-Xu He2 Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center & Sino-US Joint Laboratory for Medical Sciences, Laboratory Animal Center, Guizhou Medical University Guiyang, China.
Paul R Sanberg3 Center for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Jun Tan1 Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
University of South Florida · USAffiliated Hospital of Guizhou Medical University · CNGuiyang 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
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 AG050253NIA NIH HHS R21 AG055116
6 · The paper itself

Abstract

Alzheimer's Disease (AD) is the leading cause of dementia in the elderly. In healthy individuals, amyloid precursor protein (APP) is cleaved by α-secretase, generating soluble α-amyloid precursor protein (sAPPα), which contributes neuroprotective functions in the neuronal environment. In contrast, in the neurodegenerative environment of AD patients, amyloid-β-peptide (Aβ) of either 40 or 42 residues are generated by increased activity of β- and γ-secretase. These proteins amalgamate in specific regions of the brain, which disrupts neuronal functions and leads to cognitive impairment. Human umbilical cord blood cells (HUCBC) have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases, including AD. Our most recent work studied the impact of umbilical cord blood serum (CBS) on modulation of sAPPα production. Heat-sensitive CBS significantly promoted sAPPα production, indicating that heat-sensitive factor(s) play(s) a role in this process. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to determine the molecular source of α-secretase in purified CBS and aged blood serum (AgBS) fraction. Of the proteins identified, the subunits of C1 complex (C1q, C1r, and C1s) and alpha-2-macroglobulin showed significantly greater levels in purified α-CBS fraction (α-CBSF) compared with the AgBS fraction (AgBSF). Specifically, C1 markedly increased sAPPα and alpha-carboxyl-terminal fragment (α-CTF) production in a dose-dependent fashion, whereas C1q alone only minimally increased and C3 did not increase sAPPα production in the absence of sera. Furthermore, C1q markedly increased sAPPα and α-CTF, while decreasing Aβ, in CHO/APPwt cells cultured in the presence of whole sera. These results confirm our initial assumption that APP α-secretase activity in human blood serum is mediated by complement C1, opening a potential therapeutic modality for the future of AD.

Indexed as

AgedAgingAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAnimalsCHO CellsComplement C1Complement C3bCricetinaeCricetulusFetal BloodHot TemperatureHumansMiceProteomicsAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesComplement C1Complement C3bAlzheimer’s Diseaseamyloid precursor proteinAβcomplement C1 complexcomplement systemcord blood serumhuman umbilical cord blood cellsoluble α-amyloid precursor protein

Identifiers

PMID29871524
PMCPMC7020233
OpenAlexW2805444447

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.