Evidence map›Paper›PMID 31181293›Full record

ArticleBiochimica et biophysica acta. Molecular basis of disease2019

Novel MicroRNA-455-3p and its protective effects against abnormal APP processing and amyloid beta toxicity in Alzheimer's disease.

Subodh Kumar, Arubala P Reddy, Xiangling Yin, P Hemachandra Reddy

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

Article in Biochimica et biophysica acta. Molecular basis of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 3 pooled it
6.3field-weighted citation impact, top 3% 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

55 citing papers in PubMed, 3 syntheses or guidelines pooled it, 93 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 1 institution in 1 country.

Subodh KumarInternal Medicine Department, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, United States.
Arubala P ReddyPharmacology & Neuroscience Department, Texas Tech University Health Sciences Center, 3601 4(th) Street, MS 9424, Lubbock, TX 79430, United States.
Xiangling YinGarrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, United States.
P Hemachandra ReddyInternal Medicine Department, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, United States; Garrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, United States; Cell Biology & Biochemistry Department, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, United States; Pharmacology & Neuroscience Department, Texas Tech University Health Sciences Center, 3601 4(th) Street, MS 9424, Lubbock, TX 79430, United States; Neurology Department, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, United States; Speech, Language and Hearing Sciences Departments, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, United States; Garrison Institute on Aging, South West Campus, Texas Tech University Health Sciences Center, 6630 S. Quaker Suite E, MS 7495, Lubbock, TX 79413, United States. Electronic address: hemachandra.reddy@ttuhsc.edu.
Texas Tech University · US

Funding

Dynamin-Related Protein 1 and Mitochondrial Fragmentation in Alzheimer's DiseaseR01AG042178 · NIA · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI REDDY, P. HEMACHANDRA · 2012 to 2016
$2.0M
Voltage-Dependent Anion Channel and Neurodegeneration in Alzheimer's DiseaseR01AG047812 · NIA · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI REDDY, P. HEMACHANDRA · 2014 to 2018
$1.9M
Mitochondrial Fragmentation and Neurodegeneration in Huntington's DiseaseR01NS105473 · NINDS · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI REDDY, P. HEMACHANDRA · 2017 to 2021
$1.8M
NIA NIH HHS R01 AG042178NIA NIH HHS R01 AG047812NINDS NIH HHS R01 NS105473
6 · The paper itself

Abstract

The purpose of our study is to understand the protective role of miR-455-3p against abnormal amyloid precursor protein (APP) processing, amyloid beta (Aβ) formation, defective mitochondrial biogenesis/dynamics and synaptic damage in AD progression. In-silico analysis of miR-455-3p has identified the APP gene as a putative target. Using mutant APP cells, miR-455-3p construct, biochemical and molecular assays, immunofluorescence and transmission electron microscopy (TEM) analyses, we studied the protective effects of miR-455-3p on - 1) APP regulation, amyloid beta (Aβ)(1-40) & (1-42) levels, mitochondrial biogenesis & dynamics; 3) synaptic activities and 4) cell viability & apoptosis. Our luciferase reporter assay confirmed the binding of miR-455-3p at the 3'UTR of APP gene. Immunoblot, sandwich ELISA and immunostaining analyses revealed that the reduced levels of the mutant APP, Aβ(1-40) & Aβ(1-42), and C99 by miR-455-3p. We also found the reduced levels of mRNA and proteins of mitochondrial biogenesis (PGC1α, NRF1, NRF2, and TFAM) and synaptic genes (synaptophysin and PSD95) in mutant APP cells; on the other hand, mutant APP cells that express miR-455-3p showed increased mRNA and protein levels of biogenesis and synaptic genes. Additionally, expression of mitochondrial fission proteins (DRP1 and FIS1) were decreased while the fusion proteins (OPA1, Mfn1 and Mfn2) were increased by miR-455-3p. Our TEM analysis showed a decrease in mitochondria number and an increase in the size of mitochondrial length in mutant APP cells transfected with miR-455-3p. Based on these observations, we cautiously conclude that miR-455-3p regulate APP processing and protective against mutant APP-induced mitochondrial and synaptic abnormalities in AD.

Indexed as

3' Untranslated RegionsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAntagomirsCell Line, TumorCell SurvivalHumansMiceMicroRNAsMitochondriaMitochondrial DynamicsMutagenesisPeptide FragmentsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha3' Untranslated RegionsAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Amyloid beta-Protein PrecursorAntagomirsMicroRNAsPeptide FragmentsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaSynaptophysinAlzheimer's diseaseAmyloid betaAmyloid precursor proteinmicroRNA-455-3pMitochondrial biogenesisSynaptic proteins

Identifiers

PMID31181293
PMCPMC6688505
OpenAlexW2952537795

What OpenQuestion holds

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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.