Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/PS1 Mouse Model of Alzheimer's Disease.
Overview
- Department of Physiology, Faculty of Biomedical Sciences, University of Otago, Dunedin, New Zealand
- HeartOtago, University of Otago, Dunedin, New Zealand
- Brain Health Research Centre, University of Otago, Dunedin, New Zealand
- Department of Psychology, University of Otago, Dunedin, New Zealand
Abstract
Aim: The ryanodine receptor (RyR2) is an intracellular Ca2+ release channel which mediates numerous cellular functions across different tissues. Dysregulation of RyR2 channel activity leads to pathological Ca2+ release, which often underlies disrupted cellular signaling in disease states. In the heart, RyR2 channels forms discrete clusters and calcium release units (CRUs) which control channel activity. These structures demonstrate nanoscale remodeling in disease states associated with pathological Ca2+ release activity in the heart. Hence, these nanoscale structures are critical in regulating Ca2+ release in health and disease. RyR2 is also expressed in brain; however, whether analogous clusters and CRUs form in neurons remains unexplored.
Methods: Using super‐resolution imaging, we assessed RyR2 organization in CA1 pyramidal neurons of wild‐type mice. Furthermore, we used the APP/
Results: Here, we provide the first identification and detailed characterization of RyR2 clusters in central nervous system neurons, which are comparable to those reported in the heart. Moreover, we observed a decrease in RyR2 cluster size and reduced CRU organization in AD mice at an age associated with high plaque burden and cognitive deficits. This remodeling is analogous to that reported in pathological states in the heart.
Conclusion: Together, these findings implicate the nanoscale remodeling of RyR2 clusters and CRUs as a novel mechanism underlying Ca2+ channel dysregulation and neuronal dysfunction in AD.
Reproduced under the paper's license (CC BY), from the paper cited above.
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david_baddeley/python-microscopy
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Data
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Data Availability Statement
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- Publisher: n/a → Wiley
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 6 keywords, 11 MeSH terms, 3 funders, 47 references.
Cite
This paper
Munro, M. L., Silva, R. V., Ohline, S. M., Khaing, E. P., Chan, J. A., Ibrahim, M. F., Tausi, T. F., Abraham, W. C., & Jones, P. P. (2026). Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/
BibTeX
@article{munro2026cluste
author = {Munro, Michelle L and Silva, Ruben Vergara and Ohline, Shane M and Khaing, Ei Phyo and Chan, Joan A and Ibrahim, Mohamed F and Tausi, Tausi F and Abraham, Wickliffe C and Jones, Peter P},
title = {{Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/
journal = {Acta physiologica (Oxford, England)},
year = {2026},
month = jul,
volume = {242},
number = {7},
pages = {e70264},
publisher = {Wiley},
issn = {1748-1708},
doi = {10.1111/
url = {https://
pmid = {42249616},
pmcid = {PMC13241622}
}
RIS
TY - JOUR
AU - Munro, Michelle L
AU - Silva, Ruben Vergara
AU - Ohline, Shane M
AU - Khaing, Ei Phyo
AU - Chan, Joan A
AU - Ibrahim, Mohamed F
AU - Tausi, Tausi F
AU - Abraham, Wickliffe C
AU - Jones, Peter P
TI - Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/
T2 - Acta physiologica (Oxford, England)
J2 - Acta Physiol (Oxf)
PY - 2026
DA - 2026/
VL - 242
IS - 7
SP - e70264
SN - 1748-1708
PB - Wiley
DO - 10.1111/
UR - https://
LA - en
ER -
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