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Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux
Ding N, Song Y, Zhang Y, Yu W, Li X, Li W, Li L.. Autophagy, 2025-02-25
Topic: Brain proteins, microglia and lab models
The CGG repeat expansions in the 5'-UTR regions of certain genes have been implicated in various neurodegenerative and muscular disorders. However, the underlying pathogenic mechanisms are not well understood. In this study, we explore the role of the small molecular chaperone HSPB1 in counteracting neurodegeneration induced by poly-glycine (poly-G) aggregates. Employing a reporter system, we demonstrate that CGG repeat expansions within the 5'-UTR of the GIPC1 gene produce poly-G proteins, by repeat-associated non-AUG (RAN) translation. Through proximity labeling and subsequent mass spectrometry analysis, we characterize the composition of poly-G insoluble aggregates and reveal that these aggregates sequester key macroautophagy/autophagy receptors, SQSTM1/p62 and TOLLIP. This sequestration disrupts MAP1LC3/LC3 recruitment and impairs autophagosome formation, thereby compromising the autophagic pathway. Importantly, we show that HSPB1 facilitates the dissociation of these receptors from poly-G aggregates and consequently restores autophagic function. Overexpressing HSPB1 alleviates poly-G-induced neurodegeneration in mouse models. Taken together, these findings highlight a mechanistic basis for the neuroprotective effects of HSPB1 and suggest its potential as a therapeutic target in treating poly-G-associated neurodegenerative diseases. Abbreviations : AD: Alzheimer disease; AIF1/Iba1: allograft inflammatory factor 1; Baf A 1 : bafilomycin A 1 ; BFP: blue fluorescent protein; CQ: chloroquine; EIF2A/eIF-2α: eukaryotic translation initiation factor 2A; FRAP: fluorescence recovery after photobleaching; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFAP: glial fibrillary acidic protein; GFP: green fluorescent protein; HSPB1: heat shock protein family B (small) member 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; NOTCH2NLC: notch 2 N-terminal like C; PD: Parkinson disease; PFA: paraformaldehyde; poly-A: poly-alanine; poly-G: poly-glycine; poly-R: poly-arginine; RAN translation: repeat-associated non-AUG translation; RBFOX3/NeuN: RNA binding fox-1 homolog 3; STED: stimulated emission depletion; TARDBP/TDP-43: TAR DNA binding protein; TG: thapsigargin; TOLLIP: toll interacting protein.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ding, N., Song, Y., Zhang, Y., Yu, W., Li, X., Li, W., et al. (2025). Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux. Autophagy. https://doi.org/10.1080/15548627.2025.2466144
Vancouver
Ding N, Song Y, Zhang Y, Yu W, Li X, Li W, et al. Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux. Autophagy. 2025. doi:10.1080/15548627.2025.2466144. PMID: 39936620.
BibTeX
@article{ding2025-39936620,
author = {Ding, N. and Song, Y. and Zhang, Y. and Yu, W. and Li, X. and Li, W. and Li, L.},
title = {{Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux}},
journal = {Autophagy},
year = {2025},
doi = {10.1080/15548627.2025.2466144},
pmid = {39936620},
url = {https://doi.org/10.1080/15548627.2025.2466144}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Taken together, these findings highlight a mechanistic basis for the neuroprotective effects of HSPB1 and suggest its potential as a therapeutic target in treating poly-G-associated neurodegenerative diseases.
Why it matters
In laboratory and mouse work, the chaperone HSPB1 helped remove autophagy receptors from poly-glycine aggregates and restored autophagy, reducing poly-glycine-induced neurodegeneration. This is early mechanistic research on poly-glycine-associated disease, not a proven treatment, cure or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Autophagy) |
| Journal's citation record | 2 / 4 | Autophagy: journal h-index 240 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 12 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 12 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Lei Li: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | ShanghaiTech University: institution h-index 434 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39936620) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 36 / 100 | — |
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Read the original
- DOI: 10.1080/15548627.2025.2466144
- PubMed: 39936620
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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