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Aβ42 oligomers disrupt calcium homeostasis via Piezo1 and induce neurotoxicity in differentiated SH-SY5Y cells
Meng W, Zhang J, Zhang S, Shi Y, Wang H.. Research Square, 2026-10-29
Topic: Disease mechanisms in lab and animal studies
Plain-language summary
Alzheimer's disease (AD) exhibits an intricate and multifactorial pathogenesis. Existing research on amyloid-β (Aβ)-triggered neurotoxicity has predominantly centered on neuronal apoptosis, oxidative stress, and mitochondrial damage. The role of biomechanical signaling, a vital regulatory mechanism in neuronal physiological homeostasis and AD pathological progression, remains largely uncharacterized in the context of Aβ-mediated neurotoxicity. Here, differentiated SH-SY5Y, neuron-like cells, were used to examine the Aβ42 oligomers induced cellular mechanics alteration and the abnormal activation of mechanosensitive ion channels. Aβ42 oligomer adsorption increases cellular Young's modulus, which is associated with sustained intracellular Ca 2+ elevation mediated by Piezo1. Subsequently, the overloaded Ca 2+ induces mitochondrial dysfunction, excessive reactive oxygen species accumulation, YAP/TAZ signaling activation, cytoskeletal remodeling, dynamic changes in cellular stiffness, and finally a cell death through caspase-4-mediated non-canonical pyroptosis. These findings support an Aβ42-Piezo1-Ca 2+ -cytoskeletal remodeling axis that links altered neuronal mechanics to neurotoxicity and identify Piezo1 as a potential target for further investigation in AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Meng, W., Zhang, J., Zhang, S., Shi, Y., & Wang, H. (2026). Aβ42 oligomers disrupt calcium homeostasis via Piezo1 and induce neurotoxicity in differentiated SH-SY5Y cells. Research Square. https://doi.org/10.21203/rs.3.rs-11212419/v1
Vancouver
Meng W, Zhang J, Zhang S, Shi Y, Wang H. Aβ42 oligomers disrupt calcium homeostasis via Piezo1 and induce neurotoxicity in differentiated SH-SY5Y cells. Research Square. 2026. doi:10.21203/rs.3.rs-11212419/v1.
BibTeX
@article{meng2026-02371b89,
author = {Meng, W. and Zhang, J. and Zhang, S. and Shi, Y. and Wang, H.},
title = {{Aβ42 oligomers disrupt calcium homeostasis via Piezo1 and induce neurotoxicity in differentiated SH-SY5Y cells}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-11212419/v1},
url = {https://doi.org/10.21203/rs.3.rs-11212419/v1}
}
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Key findings
- Aβ42 oligomer adsorption increases cellular Young's modulus, which is associated with sustained intracellular Ca 2+ elevation mediated by Piezo1.
- These findings support an Aβ42-Piezo1-Ca 2+ -cytoskeletal remodeling axis that links altered neuronal mechanics to neurotoxicity and identify Piezo1 as a potential target for further investigation in AD.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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