Evidence map›Paper›PMID 37733679›Full record

ArticlePLoS genetics2023

A monocarboxylate transporter rescues frontotemporal dementia and Alzheimer's disease models.

Dongwei Xu, Alec Vincent, Andrés González-Gutiérrez, Benjamin Aleyakpo, Sharifah Anoar, Ashling Giblin, Magda L Atilano, Mirjam Adams, Dunxin Shen, Annora Thoeng and 5 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Alzheimer's disease and gut-brain axis:Frontiers in neuroscience · 2025
    Review
  7. Review
  8. Article
  9. A sodium-dependent trehalose transporter contributes to anhydrobiosis in insect cell line, Pv11.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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 2 countries.

Dongwei XuDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.
Alec VincentDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.
Andrés González-GutiérrezDepartment of Neuroscience and Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile.ORCID 0000-0002-9441-2211
Benjamin AleyakpoDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.
Sharifah AnoarDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.
Ashling GiblinDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.ORCID 0000-0001-8470-7908
Magda L AtilanoDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.ORCID 0000-0002-3819-2023
Mirjam AdamsDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.
Dunxin ShenDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.
Annora ThoengDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.ORCID 0000-0001-9722-7399
Elli TsintzasDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.
Marie MaelandDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.ORCID 0009-0009-9073-1088
Adrian M IsaacsUK Dementia Research Institute at UCL, Cruciform Building, London, United Kingdom.
Jimena SierraltaDepartment of Neuroscience and Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile.ORCID 0000-0002-0257-146X
Teresa NiccoliDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, United Kingdom.ORCID 0000-0001-9337-0411
University College London · GBUK Dementia Research Institute · GBUniversity of Chile · CLNational Hospital for Neurology and Neurosurgery · GB

Funding

Medical Research Council MR/V003585/1
6 · The paper itself

Abstract

Brains are highly metabolically active organs, consuming 20% of a person's energy at resting state. A decline in glucose metabolism is a common feature across a number of neurodegenerative diseases. Another common feature is the progressive accumulation of insoluble protein deposits, it's unclear if the two are linked. Glucose metabolism in the brain is highly coupled between neurons and glia, with glucose taken up by glia and metabolised to lactate, which is then shuttled via transporters to neurons, where it is converted back to pyruvate and fed into the TCA cycle for ATP production. Monocarboxylates are also involved in signalling, and play broad ranging roles in brain homeostasis and metabolic reprogramming. However, the role of monocarboxylates in dementia has not been tested. Here, we find that increasing pyruvate import in Drosophila neurons by over-expression of the transporter bumpel, leads to a rescue of lifespan and behavioural phenotypes in fly models of both frontotemporal dementia and Alzheimer's disease. The rescue is linked to a clearance of late stage autolysosomes, leading to degradation of toxic peptides associated with disease. We propose upregulation of pyruvate import into neurons as potentially a broad-scope therapeutic approach to increase neuronal autophagy, which could be beneficial for multiple dementias.

Indexed as

Alzheimer DiseaseFrontotemporal DementiaAnimalsDrosophilaGlucoseHumansNeurogliaPyruvic AcidGlucosePyruvic Acid

Identifiers

PMID37733679
PMCPMC10513295
OpenAlexW4386922110

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.