Evidence map›Paper›PMID 33087140›Full record

ArticleMolecular neurodegeneration2020

Aging-relevant human basal forebrain cholinergic neurons as a cell model for Alzheimer's disease.

Shuaipeng Ma, Tong Zang, Meng-Lu Liu, Chun-Li Zhang

Open access · goldAbstract read
In one paragraph

Article in Molecular neurodegeneration, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

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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

4 authors at 2 institutions in 1 country.

Shuaipeng MaDepartment of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX, 75390, USA.
Tong ZangDepartment of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX, 75390, USA.
Meng-Lu LiuDepartment of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX, 75390, USA.
Chun-Li ZhangDepartment of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX, 75390, USA. chun-li.zhang@utsouthwestern.edu.ORCID 0000-0002-2639-4605
The University of Texas Southwestern Medical Center · USSouthwestern Medical Center · US

Funding

Reprogramming reactive glial cells into functional new neurons after SCIR01NS111776 · NINDS · INDIANA UNIVERSITY INDIANAPOLIS · PI WU, WEI, ZHANG, CHUN-LI · 2020 to 2024
$2.4M
Induced Adult Neurogenesis for Parkinson's DiseaseR01NS092616 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI ZHANG, CHUN-LI · 2016 to 2020
$2.4M
In Vivo Reprogramming of NG2 Glia for NeurogenesisR01NS117065 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI ZHANG, CHUN-LI · 2020 to 2024
$2.1M
Chemical Reprogramming of Traumatic Brain InjuryR01NS099073 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI ZHANG, CHUN-LI · 2017 to 2021
$1.8M
In Vivo Reprogramming of Glial Fate for Spinal Cord RepairR01NS088095 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI ZHANG, CHUN-LI · 2014 to 2018
$1.7M
NINDS NIH HHS R01 NS088095NINDS NIH HHS R01 NS092616NINDS NIH HHS R01 NS099073NINDS NIH HHS R01 NS111776NINDS NIH HHS R01 NS117065
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) is an adult-onset mental disorder with aging as a major risk factor. Early and progressive degeneration of basal forebrain cholinergic neurons (BFCNs) contributes substantially to cognitive impairments of AD. An aging-relevant cell model of BFCNs will critically help understand AD and identify potential therapeutics. Recent studies demonstrate that induced neurons directly reprogrammed from adult human skin fibroblasts retain aging-associated features. However, human induced BFCNs (hiBFCNs) have yet to be achieved.

methodsWe examined a reprogramming procedure for the generation of aging-relevant hiBFCNs through virus-mediated expression of fate-determining transcription factors. Skin fibroblasts were obtained from healthy young persons, healthy adults and sporadic AD patients. Properties of the induced neurons were examined by immunocytochemistry, qRT-PCR, western blotting, and electrophysiology.

resultsWe established a protocol for efficient generation of hiBFCNs from adult human skin fibroblasts. They show electrophysiological properties of mature neurons and express BFCN-specific markers, such as CHAT, p75NTR, ISL1, and VACHT. As a proof-of-concept, our preliminary results further reveal that hiBFCNs from sporadic AD patients exhibit time-dependent TAU hyperphosphorylation in the soma and dysfunctional nucleocytoplasmic transport activities.

conclusionsAging-relevant BFCNs can be directly reprogrammed from human skin fibroblasts of healthy adults and sporadic AD patients. They show promises as an aging-relevant cell model for understanding AD pathology and may be employed for therapeutics identification for AD.

Indexed as

Alzheimer DiseaseBasal ForebrainCholinergic NeuronsAgingCellular Reprogramming TechniquesFibroblastsHumansAgingAlzheimer’s diseaseBFCNsFibroblastsNucleocytoplasmic transportReprogrammingTAU hyperphosphorylation

Identifiers

PMID33087140
PMCPMC7579825
OpenAlexW3093933959

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.