Evidence map›Paper›PMID 39434170›Full record

ArticleActa neuropathologica communications2024

PS1/gamma-secretase acts as rogue chaperone of glutamate transporter EAAT2/GLT-1 in Alzheimer's disease.

Florian Perrin, Lauren C Anderson, Shane P C Mitchell, Priyanka Sinha, Yuliia Turchyna, Masato Maesako, Mei C Q Houser, Can Zhang, Steven L Wagner, Rudolph E Tanzi and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

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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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Florian Perrin *Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA. fperrin@mgh.harvard.edu.
Lauren C Anderson *Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Shane P C MitchellDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Priyanka SinhaDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Yuliia TurchynaDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Masato MaesakoDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Mei C Q HouserDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Can ZhangDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Steven L WagnerDepartment of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA.
Rudolph E TanziDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Oksana BerezovskaDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA. oberezovska@mgh.harvard.edu.

Funding

TRANSGENICS AND PRESENILIN FUNCTIONP01AG015379 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI TANZI, RUDOLPH EMILE · 1998 to 2023
$51.3M
Role of PS1 in neurodegenerationR01AG044486 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BEREZOVSKA, OKSANA · 2014 to 2018
$2.5M
Characterizing the roles of novel soluble GSMs in AD pathology.R01AG055784 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI ZHANG, CAN MARTIN · 2018 to 2022
$2.1M
NIA NIH HHS AG055784NIA NIH HHS AG15379NIA NIH HHS P01 AG015379NIA NIH HHS R01 AG044486NIA NIH HHS R01 AG055784
6 · The paper itself

Abstract

The recently discovered interaction between presenilin 1 (PS1), a subunit of γ-secretase involved in amyloid-β (Aβ) peptide production, and GLT-1, the major brain glutamate transporter (EAAT2 in the human), may link two pathological aspects of Alzheimer's disease: abnormal Aβ occurrence and neuronal network hyperactivity. In the current study, we employed a FRET-based fluorescence lifetime imaging microscopy (FLIM) to characterize the PS1/GLT-1 interaction in brain tissue from sporadic AD (sAD) patients. sAD brains showed significantly less PS1/GLT-1 interaction than those with frontotemporal lobar degeneration or non-demented controls. Familial AD (fAD) PS1 mutations, inducing a "closed" PS1 conformation similar to that in sAD brain, and gamma-secretase modulators (GSMs), inducing a "relaxed" conformation, respectively reduced and increased the interaction. Furthermore, PS1 influences GLT-1 cell surface expression and homomultimer formation, acting as a chaperone but not affecting GLT-1 stability. The diminished PS1/GLT-1 interaction suggests that these functions may not work properly in AD.

Indexed as

Alzheimer DiseaseAmyloid Precursor Protein SecretasesBrainExcitatory Amino Acid Transporter 2Presenilin-1AgedAged, 80 and overFemaleFluorescence Resonance Energy TransferHEK293 CellsHumansMaleMiddle AgedMolecular ChaperonesMutationAmyloid Precursor Protein SecretasesExcitatory Amino Acid Transporter 2Molecular ChaperonesPresenilin-1PSEN1 protein, humanSLC1A2 protein, humanAlzheimer’s diseaseChaperoneEAAT2Gamma-secretaseGLT-1Glutamate transportHyperactivityPresenilin 1

Identifiers

PMID39434170
PMCPMC11492509

What OpenQuestion holds

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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.