Localization and Possible Functions of Presenilins in Brain

@article{Mcgeer1998LocalizationAP,
  title={Localization and Possible Functions of Presenilins in Brain},
  author={Patrick L. Mcgeer and Toshio Kawamata and Edith Mcgeer},
  journal={Reviews in the Neurosciences},
  year={1998},
  volume={9},
  pages={1 - 16}
}
Presenilin-1 (PS-1) is localized to chromosome 14 and presenilin-2 (PS-2) to chromosome 1. Mutations in these genes, primarily in PS-1, account for an estimated 60% of early onset familial Alzheimer's disease cases (FAD), while FAD cases account for about 10% of all Alzheimer's disease (AD) cases. The mutations are minor but are 100% penetrant, suggesting that the proteins have acquired a toxic gain in function. The proteins have multiple transmembrane domains and have been reported to be… 

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References

SHOWING 1-10 OF 83 REFERENCES
Alzheimer–associated presenilins 1 and 2 : Neuronal expression in brain and localization to intracellular membranes in mammalian cells
TLDR
Using in situ hybridization, it is demonstrated that the expression patterns of PS1 and PS2 in the brain are extremely similar to each other and that messages for both are primarily detectable in neuronal populations.
Localization of Alzheimer-associated presenilin 1 in transfected COS-7 cells.
TLDR
Immuno-electronmicroscopic and biochemical analysis indicated that presenilin 1 is localized on cellular membrane (plasma, endoplasmic reticulum, and perinuclear) in COS-7 cells overexpressing presenILin 1, suggesting a possible role of PS 1 on the cell membrane as a cell adhesion molecule.
Characterization and expression of presenilin 1 in mouse brain.
TLDR
Observations suggest that other as yet identified factors might interact with mutated presenilins to cause neurodegeneration in AD-affected areas.
Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites.
  • D. Cook, J. C. Sung, R. Doms
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
TLDR
A mutant form of PS1 linked to FAD did not differ from the wild-type protein at the light microscopic level and the model system described here will enable studies of the function ofPS1 in human neurons and the role of mutant PS1 in FAD.
Processing of presenilin 1 in brains of patients with Alzheimer's disease and controls
TLDR
To examine the metabolism of PS1 in brains of patients with AD harbouring PS1 mutations I143T and G384A, immunoblot analyses of brain homogenates using well characterized antibodies document that ∼27–28 kDa N-terminal and ∼18 kDa C-Terminal PS1 proteolytic fragments accumulate in brain of these individuals, and that in large part the accumulation pattern is indistinguishable from that observed in brains from individuals with sporadic AD or controls.
Expression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues
TLDR
Examination of the expression of PS1 and PS2 mRNA and PS1 protein in human and mouse tissues revealed that PS 1 protein accumulates in a variety of neuronal populations with enrichment in somatodendritic and neuropil compartments, and it is demonstrated that PS1 accumulates as ∼28 kDa N-terminal and ∼18 kDa C-Terminal fragments in brain.
Hyperaccumulation of FAD-linked presenilin 1 variants in vivo
TLDR
It is document that, in the brains of transgenic mice, the absolute amounts of accumulated N- and C-terminal derivatives generated from the FAD-linked PS1 variants in which Glu replaces Ala at codon 246 (A246E) or Leu replaces Met atcodon 146 (M146L) accumulate to a significantly higher degree than the fragments derived from wild-type PS1.
Presenilin-1 is associated with Alzheimer's disease amyloid.
TLDR
Three of the proteins with linkage to AD have now been found as components of neuritic plaques, and it remains to be determined whether all of these proteins are involved in the same or different pathological pathway(s) and which ofThese proteins is the most important for the common, late-onset form of AD.
...
1
2
3
4
5
...