Evidence map›Paper›PMID 35455952›Full record

ArticleCells2022

Lysosomes Dysfunction Causes Mitophagy Impairment in PBMCs of Sporadic ALS Patients.

Matteo Bordoni, Orietta Pansarasa, Eveljn Scarian, Riccardo Cristofani, Roberta Leone, Valentina Fantini, Maria Garofalo, Luca Diamanti, Stefano Bernuzzi, Stella Gagliardi and 3 more

Abstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
–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

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

12 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Trimetazidine Improves Mitochondrial Dysfunction in SOD1International journal of molecular sciences · 2024
    Article
  10. Review
  11. Review
  12. 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

13 authors.

Matteo BordoniGenomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.ORCID 0000-0001-9461-756X
Orietta PansarasaGenomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.ORCID 0000-0002-3041-0612
Eveljn ScarianGenomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.ORCID 0000-0002-6703-1755
Riccardo CristofaniDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Università Degli Studi di Milano, 20133 Milano, Italy.ORCID 0000-0003-2719-846X
Roberta LeoneCasa di Cura Ars Medica S.p.a, 00191 Rome, Italy.
Valentina FantiniLaboratory of Neurobiology and Neurogenetic, Golgi-Cenci Foundation, 20081 Abbiategrasso, Italy.ORCID 0000-0003-1244-4453
Maria GarofaloGenomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.ORCID 0000-0002-8668-3855
Luca DiamantiNeuroncology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.
Stefano BernuzziImmunohematological and Transfusional Service and Centre of Transplantation Immunology, IRCCS "San Matteo Foundation", 27100 Pavia, Italy.
Stella GagliardiGenomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.ORCID 0000-0002-6589-6907
Stephana CarelliDepartment of Biomedical and Clinical Sciences "L. Sacco", University of Milan, 20157 Milan, Italy.ORCID 0000-0003-4603-396X
Angelo PolettiDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Università Degli Studi di Milano, 20133 Milano, Italy.ORCID 0000-0002-8883-0468
Cristina CeredaGenomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.ORCID 0000-0001-9571-0862

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitochondria alterations are present in tissues derived from patients and animal models, but no data are available for peripheral blood mononuclear cells (PBMCs) of ALS patients. This work aims to investigate mitophagy in PBMCs of sporadic (sALS) patients and how this pathway can be tuned by using small molecules. We found the presence of morphologically atypical mitochondria by TEM and morphological abnormalities by MitoTracker™. We found a decreased number of healthy mitochondria in sALS PBMCs and an impairment of mitophagy with western blot and immunofluorescence. After rapamycin treatment, we found a higher increase in the LC3 marker in sALS PBMCs, while after NH4Cl treatment, we found a lower increase in the LC3 marker. Finally, mTOR-independent autophagy induction with trehalose resulted in a significant decrease in the lysosomes level sALS PBMCs. Our data suggest that the presence of morphologically altered mitochondria and an inefficient turnover of damaged mitochondria in PBMCs of sALS patients rely on the impairment of the mitophagy pathway. We also found that the induction of the mTOR-independent autophagy pathway leads to a decrease in lysosomes level, suggesting a more sensitivity of sALS PBMCs to trehalose. Such evidence suggests that trehalose could represent an effective treatment for ALS patients.

Indexed as

Amyotrophic Lateral SclerosisMitophagyAnimalsHumansLeukocytes, MononuclearLysosomesTOR Serine-Threonine KinasesTrehaloseTOR Serine-Threonine KinasesTrehaloseALSautolysosomesmitochondriamTORPBMCstrehalose

Identifiers

PMID35455952
PMCPMC9030813

What OpenQuestion 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 OpenQuestion graph.