Neurons bearing presenilins: weapons for defense or suicide?
B. O. Popescu1, Maria Ankarcrona
1Karolinska Institutet, NEUROTEC, Section for Geriatric Medicine, NOVUM, KFC, 4th floor, S-141 86 Huddinge, Sweden. Bogdan.Popescu@kfcmail.hs.sll.se
Abstract:
Apoptotic machinery designed for cell's organized self-destruction involve different systems of proteases which cleave vital proteins and disassemble nuclear and cytoplasmic structures, committing the cell to death. The most studied apoptotic proteolytic system is the caspase family, but calpains and the proteasome could play important roles as well. Alzheimer's disease associated presenilins showed to be a substrate for such proteolytic systems, being processed early in several apoptotic models, and recent data suggest that alternative presenilin fragments could regulate cell survival. Mutations in genes encoding presenilins proved to sensitize neurons to apoptosis by different mechanisms e.g. increased caspase-3 activation, oxyradicals production and calcium signaling dysregulation. Here we review the data involving presenilins in apoptosis and discuss a possible role of presenilins in the regulation of apoptotic biochemical machinery.
Insights
Presenilins are implicated in programmed cell death (apoptosis) and Alzheimer's disease. This review explores presenilins' role in regulating apoptotic machinery and neuronal survival.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- Apoptosis involves protease systems like caspases, calpains, and the proteasome, crucial for cellular self-destruction.
- Presenilins, linked to Alzheimer's disease, are processed by these proteolytic systems during apoptosis.
- Dysfunctional presenilins can increase neuronal vulnerability to apoptosis through various mechanisms.
Purpose of the Study:
- To review the involvement of presenilins in apoptosis.
- To discuss the potential role of presenilins in regulating the biochemical machinery of apoptosis.
- To explore how presenilin mutations affect neuronal apoptosis.
Main Methods:
- Literature review of studies on presenilins and apoptosis.
- Analysis of data linking presenilin processing to apoptotic pathways.
- Examination of evidence for presenilin fragments in cell survival regulation.
Main Results:
- Presenilins are early substrates in apoptotic models.
- Alternative presenilin fragments may influence cell survival.
- Presenilin gene mutations sensitize neurons to apoptosis via caspase activation, oxidative stress, and calcium dysregulation.
Conclusions:
- Presenilins play a significant role in the apoptotic process.
- Presenilins are potential regulators of the cell's self-destruction machinery.
- Understanding presenilin's role in apoptosis is crucial for Alzheimer's disease research.
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