Presenilins in synaptic function and disease.
Open accessAbstract
The presenilin genes harbor approximately 90% of mutations linked to early-onset familial Alzheimer's disease (FAD), but how these mutations cause the disease is still being debated. Genetic analysis in Drosophila and mice demonstrate that presenilin plays essential roles in synaptic function, learning and memory, as well as neuronal survival in the adult brain, and the FAD-linked mutations alter the normal function of presenilin in these processes. Presenilin has also been reported to regulate the calcium homeostasis of intracellular stores, and presynaptic presenilin controls neurotransmitter release and long-term potentiation through modulation of calcium release from intracellular stores. In this review, we highlight recent advances in deciphering the role of presenilin in synaptic function, calcium regulation and disease, and pose key questions for future studies.
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Previous evidence indicates that presenilins influence synaptic function and intracellular calcium homeostasis.
“This broad and mixed response is consistent with the wider perturbation of interleukin, TGF-β, Wnt, glutamatergic, and presenilin signaling observed in our pathway analysis and with previous evidence that presenilins influence synaptic function and intracellular calcium homeostasis (Ho and Shen, 2011; Shen and Kelleher, 2007).”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Ho and Shen, 2011
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- Authors
- Ho, A., & Shen, J.
- Affiliations
- Boston University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Shen, Jie
- ORCID
- Shen, Jie
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 17
- Issue
- 11
- Pages
- 617-624
- ISSN
- 1471-4914 (ISSN-L)
- PMC
- PMC3205282
- OpenAlex
- W2073660598
- Cited by
- 52
- References
- 64
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 4 · 2015: 1 · 2014: 7 · 2013: 15 · 2012: 5
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (K01AG027311)
- National Institute of Neurological Disorders and Stroke (NS041783, RF1NS041783, R01NS042818, NS042818, R01NS041783)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- presenilin, presenilin mutations, early-onset familial Alzheimer's disease, synaptic function, learning and memory, neuronal survival, calcium homeostasis, intracellular calcium stores, presynaptic neurotransmitter release, long-term potentiation, Drosophila, mouse model
- MeSH terms
- Alzheimer Disease, Animals, Calcium, Cerebral Cortex, Homeostasis, Humans, Synapses, Mutation, Missense, Presenilin-1
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