Back to Search
Start Over
Familial Alzheimer’s disease presenilin-2 mutants affect Ca2+ homeostasis and brain network excitability
- Source :
- Aging Clinical and Experimental Research. 33:1705-1708
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Alzheimer's disease (AD) is the most frequent cause of dementia in the elderly. Few cases are familial (FAD), due to autosomal dominant mutations in presenilin-1 (PS1), presenilin-2 (PS2) or amyloid precursor protein (APP). The three proteins are involved in the generation of amyloid-beta (Aβ) peptides, providing genetic support to the hypothesis of Aβ pathogenicity. However, clinical trials focused on the Aβ pathway failed in their attempt to modify disease progression, suggesting the existence of additional pathogenic mechanisms. Ca2+ dysregulation is a feature of cerebral aging, with an increased frequency and anticipated age of onset in several forms of neurodegeneration, including AD. Interestingly, FAD-linked PS1 and PS2 mutants alter multiple key cellular pathways, including Ca2+ signaling. By generating novel tools for measuring Ca2+ in living cells, and combining different approaches, we showed that FAD-linked PS2 mutants significantly alter cell Ca2+ signaling and brain network activity, as summarized below.
- Subjects :
- Aging
Amyloid beta
Cell
Mutant
Presenilin
Alzheimer’s disease
Amyloid-beta
Brain network
Ca2+ probes
Calcium homeostasis
03 medical and health sciences
0302 clinical medicine
mental disorders
medicine
Amyloid precursor protein
Dementia
030212 general & internal medicine
biology
Neurodegeneration
medicine.disease
medicine.anatomical_structure
biology.protein
Geriatrics and Gerontology
Age of onset
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 17208319
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Aging Clinical and Experimental Research
- Accession number :
- edsair.doi.dedup.....8f075f9484575d3a5d2f03df1e1cb4ca