Evidence map›Paper›PMID 33203136›Full record

ArticleCells2020

Presynaptic Vesicle Protein SEPTIN5 Regulates the Degradation of APP C-Terminal Fragments and the Levels of Aβ.

Mikael Marttinen, Catarina B Ferreira, Kaisa M A Paldanius, Mari Takalo, Teemu Natunen, Petra Mäkinen, Luukas Leppänen, Ville Leinonen, Kenji Tanigaki, Gina Kang and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

10 citing papers in PubMed, 11 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

15 authors at 4 institutions in 4 countries.

Mikael MarttinenInstitute of Biomedicine, University of Eastern Finland, 70210 Kuopio, Finland.
Catarina B FerreiraInstituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Kaisa M A PaldaniusInstitute of Biomedicine, University of Eastern Finland, 70210 Kuopio, Finland.
Mari TakaloInstitute of Biomedicine, University of Eastern Finland, 70210 Kuopio, Finland.
Teemu NatunenInstitute of Biomedicine, University of Eastern Finland, 70210 Kuopio, Finland.
Petra MäkinenInstitute of Biomedicine, University of Eastern Finland, 70210 Kuopio, Finland.
Luukas LeppänenInstitute of Biomedicine, University of Eastern Finland, 70210 Kuopio, Finland.
Ville LeinonenInstitute of Clinical Medicine-Neurosurgery, University of Eastern Finland, 70210 Kuopio, Finland.ORCID 0000-0002-4282-4687
Kenji TanigakiResearch Institute, Shiga Medical Center, Shiga 524-8524, Japan.
Gina KangDepartment of Pharmacology, Department of Integrative and Systems Physiology, Department of Cell Systems and Anatomy, Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX 77030, USA.
Noboru HiroiDepartment of Pharmacology, Department of Integrative and Systems Physiology, Department of Cell Systems and Anatomy, Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX 77030, USA.
Hilkka SoininenInstitute of Clinical Medicine-Neurology, University of Eastern Finland, 70210 Kuopio, Finland.ORCID 0000-0002-2785-9937
Kirsi RillaInstitute of Biomedicine, University of Eastern Finland, 70210 Kuopio, Finland.ORCID 0000-0002-7862-5727
Annakaisa HaapasaloA.I Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland.ORCID 0000-0003-0959-2957
Mikko HiltunenInstitute of Biomedicine, University of Eastern Finland, 70210 Kuopio, Finland.ORCID 0000-0003-3566-4096
University of Eastern Finland · FIThe University of Texas Health Science Center at San Antonio · USShiga Medical Center · JPUniversity of Lisbon · PT

Funding

Support for the Rose F. Kennedy IDDRCU54HD090260 · NICHD · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI GREALLY, JOHN · 2016 to 2020
$6.0M
Postnatal mechanisms of cognitive development in miceR01MH099660 · NIMH · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Noboru Hiroi · 2013 to 2026
$5.9M
Structure and Function of Neonatal Social Communication in Genetic Mouse Models of AutismR01DC015776 · NIDCD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HIROI, NOBORU · 2017 to 2021
$1.7M
22q11 Genes and Complex Behavior in MiceR21HD053114 · NICHD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI HIROI, NOBORU · 2008 to 2009
$453k
NICHD NIH HHS R21 HD053114NICHD NIH HHS U54 HD090260NIDCD NIH HHS R01 DC015776NIMH NIH HHS R01 MH099660
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by aberrant amyloid-β (Aβ) and hyperphosphorylated tau aggregation. We have previously investigated the involvement of SEPTIN family members in AD-related cellular processes and discovered a role for SEPTIN8 in the sorting and accumulation of β-secretase. Here, we elucidated the potential role of SEPTIN5, an interaction partner of SEPTIN8, in the cellular processes relevant for AD, including amyloid precursor protein (APP) processing and the generation of Aβ. The in vitro and in vivo studies both revealed that the downregulation of SEPTIN5 reduced the levels of APP C-terminal fragments (APP CTFs) and Aβ in neuronal cells and in the cortex of Septin5 knockout mice. Mechanistic elucidation revealed that the downregulation of SEPTIN5 increased the degradation of APP CTFs, without affecting the secretory pathway-related trafficking or the endocytosis of APP. Furthermore, we found that the APP CTFs were degraded, to a large extent, via the autophagosomal pathway and that the downregulation of SEPTIN5 enhanced autophagosomal activity in neuronal cells as indicated by altered levels of key autophagosomal markers. Collectively, our data suggest that the downregulation of SEPTIN5 increases the autophagy-mediated degradation of APP CTFs, leading to reduced levels of Aβ in neuronal cells.

Indexed as

Amyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAutophagyBrainCell Cycle ProteinsEndocytosisHumansMiceMice, KnockoutNeurodegenerative DiseasesNeuronsPeptide FragmentsProtein TransportSeptinsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorCell Cycle ProteinsPeptide FragmentsSept5 protein, mouseSEPTIN5 protein, humanSeptinsAlzheimer’s diseaseAPP C-terminal fragmentsautophagyAβSEPTIN5

Identifiers

PMID33203136
PMCPMC7696542
OpenAlexW3102302164

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.