Evidence map›Paper›PMID 35883623›Full record

ArticleCells2022

Modulation of MAPK- and PI3/AKT-Dependent Autophagy Signaling by Stavudine (D4T) in PBMC of Alzheimer's Disease Patients.

Francesca La Rosa, Chiara Paola Zoia, Chiara Bazzini, Alessandra Bolognini, Marina Saresella, Elisa Conti, Carlo Ferrarese, Federica Piancone, Ivana Marventano, Daniela Galimberti and 3 more

Open access · goldAbstract 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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. International journal of molecular sciences · 2025
    Article
  3. Article
  4. Article
  5. Unravelling the plasma proteome: Pioneering biomarkers for differential dementia diagnosis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. TREM2 Expression and Amyloid-Beta Phagocytosis in Alzheimer's Disease.International journal of molecular sciences · 2023
    Article
  12. Article
  13. Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Review
  14. Article
  15. Article
  16. Review
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 at 4 institutions in 1 country.

Francesca La RosaIRCCS Fondazione Don Carlo Gnocchi, 20148 Milano, Italy.ORCID 0000-0003-3181-9505
Chiara Paola ZoiaNeurobiology Laboratory, School of Medicine, University of Study of Milano-Bicocca, 20900 Monza, Italy.ORCID 0000-0003-1654-4996
Chiara BazziniNeurobiology Laboratory, School of Medicine, University of Study of Milano-Bicocca, 20900 Monza, Italy.ORCID 0000-0003-2673-5913
Alessandra BologniniNeurobiology Laboratory, School of Medicine, University of Study of Milano-Bicocca, 20900 Monza, Italy.
Marina SaresellaIRCCS Fondazione Don Carlo Gnocchi, 20148 Milano, Italy.
Elisa ContiNeurobiology Laboratory, School of Medicine, University of Study of Milano-Bicocca, 20900 Monza, Italy.ORCID 0000-0002-8308-9084
Carlo FerrareseNeurobiology Laboratory, School of Medicine, University of Study of Milano-Bicocca, 20900 Monza, Italy.
Federica PianconeIRCCS Fondazione Don Carlo Gnocchi, 20148 Milano, Italy.
Ivana MarventanoIRCCS Fondazione Don Carlo Gnocchi, 20148 Milano, Italy.
Daniela GalimbertiFondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy.ORCID 0000-0002-9284-5953
Chiara FenoglioDepartment of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy.
Elio ScarpiniFondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Mario ClericiIRCCS Fondazione Don Carlo Gnocchi, 20148 Milano, Italy.
Don Carlo Gnocchi Foundation · ITUniversity of Milan · ITUniversity of Milano-Bicocca · ITAzienda Ospedaliera San Gerardo · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAβ

methodsWe explored the effect of D4T on Aβ autophagy in PBMC from AD patients that were primed with LPS and stimulated with Aβ oligomers in the absence/presence of D4T. We analyzed the NLRP3 activity by measuring NLRP3-ASC complex formation by AMNIS FlowSight and pro-inflammatory cytokine (IL-1β, IL-18 and Caspase-1) production by ELISA. The phosphorylation status of p38, ERK, AKT, p70, and the protein expression of CREB, LAMP2A, beclin-1, Caspase-3 and Bcl2 were analyzed by Western blot.

resultsData showed that D4T: (1) downregulates NLRP3 inflammasome activation and the production of down-stream pro-inflammatory cytokines in PBMC; (2) stimulates the phosphorylation of AKT, ERK and p70 as well as LAMP2A, beclin-1 and Bcl2 expression and reduces Caspase-3 expression, suggesting an effect of this compound on autophagy; (3) increases phospho-CREB, which is a downstream target of p-ERK and p-AKT, inducing anti-inflammatory cytokine production and resulting in a possible decrease of Aβ-mediated cytotoxicity; and (4) reduces the phosphorylation of p38, a protein involved in the production of pro-inflammatory cytokines and tau hyperphosphorylation.

conclusionsD4T reduces the activation of the NLRP3 inflammasome, and it might stimulate autophagy as well as the molecular mechanism that modulates Aβ cytotoxicity, and D4T might reduce inflammation in the cells of AD patients. It could be very interesting to check the possible beneficial effects of D4T in the clinical scenario.

Indexed as

Alzheimer DiseaseInflammasomesAmyloid beta-PeptidesAutophagyBeclin-1Caspase 3CytokinesHumansLeukocytes, MononuclearNLR Family, Pyrin Domain-Containing 3 ProteinPlaque, AmyloidProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-bcl-2StavudineAmyloid beta-PeptidesBeclin-1Caspase 3CytokinesInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-bcl-2Stavudineamyloid-βcaspase-3 and Bcl2ERKneuroinflammationNLRP3-inflammasomep38p70S6K and CREB phosphorylation

Identifiers

PMID35883623
PMCPMC9322713
OpenAlexW4285088828

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.