Evidence map›Paper›PMID 39289391›Full record

ArticleNature communications2024

Structural basis of CDNF interaction with the UPR regulator GRP78.

Melissa A Graewert, Maria Volkova, Klara Jonasson, Juha A E Määttä, Tobias Gräwert, Samara Mamidi, Natalia Kulesskaya, Johan Evenäs, Richard E Johnsson, Dmitri Svergun and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. 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

12 authors.

Melissa A GraewertEuropean Molecular Biological Laboratory, DE-22607, Hamburg, Germany.ORCID 0000-0001-7547-636X
Maria VolkovaRed Glead Discovery AB, Medicon Village SE-223 81, Lund, Sweden.ORCID 0009-0000-3021-8586
Klara JonassonRed Glead Discovery AB, Medicon Village SE-223 81, Lund, Sweden.
Juha A E MäättäFaculty of Medicine and Health Technology, Tampere University, Tampere, FI-33520, Finland.
Tobias GräwertBIOSAXS GmbH, DE-22607, Hamburg, Germany.
Samara MamidiRed Glead Discovery AB, Medicon Village SE-223 81, Lund, Sweden.
Natalia KulesskayaHerantis Pharma Plc, FI-02600, Espoo, Finland.ORCID 0000-0001-5517-8525
Johan EvenäsRed Glead Discovery AB, Medicon Village SE-223 81, Lund, Sweden.
Richard E JohnssonRed Glead Discovery AB, Medicon Village SE-223 81, Lund, Sweden.
Dmitri SvergunBIOSAXS GmbH, DE-22607, Hamburg, Germany.
Arnab Bhattacharjee *Herantis Pharma Plc, FI-02600, Espoo, Finland. arnab.bhattacharjee@gmx.com.ORCID 0000-0002-9613-7911
Henri J Huttunen *Herantis Pharma Plc, FI-02600, Espoo, Finland. henri.huttunen@herantis.com.ORCID 0000-0002-9867-4438

Funding

EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 871037
6 · The paper itself

Abstract

Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that is a disease-modifying drug candidate for Parkinson's disease. CDNF has pleiotropic protective effects on stressed cells, but its mechanism of action remains incompletely understood. Here, we use state-of-the-art advanced structural techniques to resolve the structural basis of CDNF interaction with GRP78, the master regulator of the unfolded protein response (UPR) pathway. Subsequent binding studies confirm the obtained structural model of the complex, eventually revealing the interaction site of CDNF and GRP78. Finally, mutating the key residues of CDNF mediating its interaction with GRP78 not only results in impaired binding of CDNF but also abolishes the neuroprotective activity of CDNF-derived peptides in mesencephalic neuron cultures. These results suggest that the molecular interaction with GRP78 mediates the neuroprotective actions of CDNF and provide a structural basis for development of next generation CDNF-based therapeutic compounds against neurodegenerative diseases.

Indexed as

Endoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsUnfolded Protein ResponseAnimalsBinding SitesHumansModels, MolecularNerve Growth FactorsNeuronsNeuroprotective AgentsProtein BindingCDNF protein, humanEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHSPA5 protein, humanNerve Growth FactorsNeuroprotective Agents

Identifiers

PMID39289391
PMCPMC11408689

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.