A newly identified cell death mechanism, named karyoptosis, may be the missing link explaining how neurons are lost in Alzheimer's disease and frontotemporal dementia.
Scientists at King's College London, in collaboration with the UK Dementia Research Institute and funded by Alzheimer's Research UK, have pinpointed a new biological process driving brain cell death. Published in Nature Communications, the study analyzed 3,000 cells from 28 patient brains, revealing a stark biological divide.
A striking 35% of frontal cortex cells from Alzheimer's patients showed signs of karyoptosis, compared to just 15% in healthy aged controls.
What is Karyoptosis?
Karyoptosis is described as a series of chemical reactions triggered by the accumulation of toxic proteins. The process is distinctly physical:
- The Mechanism: Toxic proteins destabilize the nucleus's outer envelope.
- The Result: This causes the nucleus to shrivel and eventually disintegrate, leading to cell death.
A Potential Therapeutic Target
The research also opens a new avenue for intervention. Targeting the specific interaction between p38 MAP kinase and LaminB1 was found to reduce markers of karyoptosis in rat neurons in vitro.
This discovery suggests that interrupting this chemical handshake could potentially halt the nuclear breakdown, making it a promising target for future drug development.
Study Support
This research was made possible through funding from Alzheimer's Research UK, the Biotechnology and Biological Sciences Research Council International Partnership, the UK Medical Research Council, and the UK Dementia Research Institute.