Evidence map›Paper›PMID 41651422›Full record

ArticleThe Journal of biological chemistry2026

HSP-1-specific nanobodies alter chaperone function in vitro and in vivo.

Nicholas D Urban, Kunal Gharat, Zachary J Mattiola, Ashley Scheutzow, Adam Klaiss, Sarah Tabler, Asa W Huffaker, Monique Grootveld, Mary E Skinner, Weiyang Zheng and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Nicholas D UrbanDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Kunal GharatLeibniz Institute on Aging - Fritz-Lipmann-Institute (FLI), Jena, Germany.
Zachary J MattiolaDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Ashley ScheutzowDepartment of Biochemistry, University of Michigan, Ann Arbor, Michigan, USA.
Adam KlaissDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Sarah TablerDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Asa W HuffakerDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Monique GrootveldSanquin, CX Amsterdam.
Mary E SkinnerDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Weiyang ZhengGilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
Matthew J O'MearaGilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA.
Janine KirsteinLeibniz Institute on Aging - Fritz-Lipmann-Institute (FLI), Jena, Germany; Friedrich-Schiller-Universität, Institute for Biochemistry and Biophysics, Jena, Germany.
Matthias C TruttmannDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA; Geriatrics Center, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: mtruttma@med.umich.edu.

Funding

Learning How to Give Casual Explanations for Large Scale Virtual and Morphological PharmacologyR35GM151129 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Matthew J O'Meara · 2023 to 2026
$1.5M
NIGMS NIH HHS R35 GM151129
6 · The paper itself

Abstract

Targeted regulation of 70 kDa heat shock protein (HSP70) chaperones, particularly the essential cognate heat shock protein (HSC70) and its Caenorhabditis elegans ortholog (HSP-1), may hold the key to improving cellular proteostasis and ameliorating aging-associated conditions linked to protein misfolding and aggregation. However, tools to selectively alter HSP70 chaperone activity remain elusive. In this study, we pioneer the development of two novel nanobodies, B12 and H5, which specifically bind to both recombinant and endogenous HSP-1. We show that these nanobodies, differing by only two amino acids in their complementarity-determining regions, bind specifically to HSP-1 and effectively reduce both HSP-1 ATPase activity and protein folding capacity in a dose-dependent manner in vitro. We further demonstrate in vivo expression of B12, but not H5, in transgenic C. elegans strains reduces heat-stress survival and proteotoxic-stress resistance, mirroring the effects of hsp-1 knockdown via RNA interference. Our findings suggest that these nanobodies can serve as effective and specific tools for inhibiting HSP-1 chaperone activity in vivo. These discoveries provide a foundation for future research exploring the therapeutic potential of HSP70-targeting nanobodies in aging and protein misfolding diseases.

Indexed as

Caenorhabditis elegans ProteinsHSP70 Heat-Shock ProteinsSingle-Domain AntibodiesAnimalsCaenorhabditis elegansProtein FoldingProteotoxic StressCaenorhabditis elegans ProteinsHSP70 Heat-Shock ProteinsSingle-Domain AntibodiesC. eleganschaperoneheat shock proteinHSC70HSP-1HSP70nanobodyproteostasis

Identifiers

PMID41651422
PMCPMC12966735

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.