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Familial Alzheimer’s disease–associated presenilin 1 mutants promote γ-secretase cleavage of STIM1 to impair store-operated Ca 2+ entry
Abstract
Excess cleavage of STIM1 may underlie calcium homeostasis defects that contribute to memory loss in Alzheimer’s disease.
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“Functionally, the PSEN1 M146L mutation has been shown to enhance γ-secretase activity toward noncanonical substrates, including increased cleavage of the endoplasmic reticulum calcium sensor STIM1, thereby implicating dysregulated calcium homeostasis in disease progression (Tong et al. 2016).”
From TMEM55B downregulation promotes neurodegeneration in Alzheimer’s disease models (2026) · cites this paper as Tong et al. 2016
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Lessons from a failed γ-secretase Alzheimer trial
De Strooper, B. (2014) · Cell · doi:10.1016/j.cell.2014.10.016 · Cited by 277
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Cited by
Sorted by citations
Critical review: involvement of endoplasmic reticulum stress in the aetiology of Alzheimer's disease
Hashimoto, S., & Saido, T. C. (2018) · Open Biology · doi:10.1098/rsob.180024 · Cited by 129
Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer’s Disease
McDaid, J., Mustaly-Kalimi, S., & Stutzmann, G. E. (2020) · Cells · doi:10.3390/cells9122655 · Cited by 73
Tong, B. C.-K., Wu, A. J., Huang, A. S., Dong, R., Malampati, S., Iyaswamy, A., Krishnamoorthi, S., Sreenivasmurthy, S. G., Zhu, Z., Su, C., et al. (2022) · Autophagy · doi:10.1080/15548627.2021.1945220 · Cited by 49
Self-citationTMEM55B downregulation promotes neurodegeneration in Alzheimer’s disease models
Roy, B., Contu, V. R., Jeziorek, M., Friedman, W. J., & Wong, C.-O. (2026) · doi:10.64898/2026.10.21.760809
Metadata
- Authors
- Tong, B. C.-K., Lee, C. S.-K., Cheng, W.-H., Lai, K.-O., Kevin Foskett, J., & Cheung, K.-H.
- Affiliations
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
- Departments of Physiology and Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
- Venue
- Science Signaling
- Published
- 2016-09-06
- Volume
- 9
- Issue
- 444
- ISSN
- 1945-0877
- 1937-9145
- PMC
- PMC5384262
- Cited by
- 87
- References
- 3
- Language
- en
- Funders
- General Research Fund of Hong Kong (HKU763811M)
- National Natural Science Foundation of China (31200883)
- Seed Funding for Basic Sciences of the University of Hong Kong (2.01E+11)
- NIH (MH059937)
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