Evidence map›Paper›PMID 30707393›Full record

ArticleMolecular neurobiology2019

Upregulation of Proteolytic Pathways and Altered Protein Biosynthesis Underlie Retinal Pathology in a Mouse Model of Alzheimer's Disease.

Mehdi Mirzaei, Kanishka Pushpitha, Liting Deng, Nitin Chitranshi, Veer Gupta, Rashi Rajput, Abu Bakr Mangani, Yogita Dheer, Angela Godinez, Matthew J McKay and 8 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 2 pooled it
4.3field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 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

18 authors at 4 institutions in 2 countries.

Mehdi MirzaeiDepartment of Molecular Sciences, Macquarie University, Sydney, NSW, Australia. mehdi.mirzaei@mq.edu.au.
Kanishka PushpithaFaculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Liting DengDepartment of Molecular Sciences, Macquarie University, Sydney, NSW, Australia.
Nitin ChitranshiFaculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Veer GuptaSchool of Medicine, Deakin University, Melbourne, VIC, Australia.
Rashi RajputFaculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Abu Bakr ManganiFaculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Yogita DheerFaculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Angela GodinezFaculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Matthew J McKayDepartment of Molecular Sciences, Macquarie University, Sydney, NSW, Australia.
Karthik KamathDepartment of Molecular Sciences, Macquarie University, Sydney, NSW, Australia.
Dana PascoviciDepartment of Molecular Sciences, Macquarie University, Sydney, NSW, Australia.
Jemma X WuDepartment of Molecular Sciences, Macquarie University, Sydney, NSW, Australia.
Ghasem Hosseini SalekdehDepartment of Molecular Sciences, Macquarie University, Sydney, NSW, Australia.
Tim KarlSchool of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
Paul A HaynesDepartment of Molecular Sciences, Macquarie University, Sydney, NSW, Australia.
Stuart L GrahamFaculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Vivek K GuptaFaculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia. vivek.gupta@mq.edu.au.
Macquarie University · AUAustralian Genome Research Facility · AUDeakin University · AUCamden and Campbelltown Hospitals · AU

Funding

Macquarie University 5016420National Health and Medical Research Council 1084767The Ophthalmic Research Institute of Australia 9201400700
6 · The paper itself

Abstract

Increased amyloid β (Aβ) aggregation is a hallmark feature of Alzheimer's disease (AD) pathology. The APP/PS1 mouse model of AD exhibits accumulation of Aβ in the retina and demonstrates reduced retinal function and other degenerative changes. The overall molecular effects of AD pathology on the retina remain undetermined. Using a proteomics approach, this study assessed the molecular effects of Aβ accumulation and progression of AD pathology on the retina. Retinal tissues from younger (2.5 months) and older 8-month APP/PS1 mice were analysed for protein expression changes. A multiplexed proteomics approach using chemical isobaric tandem mass tags was applied followed by functional and protein-protein interaction analyses using Ingenuity pathway (IPA) and STRING computational tools. We identified approximately 2000 proteins each in the younger (upregulated 50; downregulated 36) and older set of APP/PS1 (upregulated 85; downregulated 79) mice retinas. Amyloid precursor protein (APP) was consistently upregulated two to threefold in both younger and older retinas (p < 0.0001). Mass spectrometry data further revealed that older APP/PS1 mice retinas had elevated levels of proteolytic enzymes cathepsin D, presenilin 2 and nicastrin that are associated with APP processing. Increased levels of proteasomal proteins Psma5, Psmd3 and Psmb2 were also observed in the older AD retinas. In contrast to the younger animals, significant downregulation of protein synthesis and elongation associated proteins such as Eef1a1, Rpl35a, Mrpl2 and Eef1e1 (p < 0.04) was identified in the older mice retinas. This study reports for the first time that not only old but also young APP/PS1 animals demonstrate increased amyloid protein levels in their retinas. Quantitative proteomics reveals new molecular insights which may represent a cellular response to clear amyloid build-up. Further, downregulation of ribosomal proteins involved in protein biosynthesis was observed which might be considered a toxicity effect.

Indexed as

Protein BiosynthesisProteolysisUp-RegulationAgingalpha-Crystallin B ChainAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsDisease Models, AnimalDown-RegulationHumansMice, Inbred C57BLMice, TransgenicPresenilin-1Proteasome Endopeptidase ComplexProtein Interaction Mapsalpha-Crystallin B ChainAmyloid beta-Protein PrecursorPresenilin-1Proteasome Endopeptidase ComplexAlzheimer's diseaseAmyloid betaAPP/PS1Quantitative proteomicsRetinaTandem mass tag

Identifiers

PMID30707393
OpenAlexW2913586680

What OpenQuestion holds

Textmetadata
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.