"By specifically targeting the interaction between p38 MAP kinase and LaminB1 we may slow down the process of cell death, buying time for more pinpointed therapies."
— Dr. Manolis Fanto, King's College London
A New Form of Cell Death Discovered in Alzheimer’s and FTD
A study published in Nature Communications has identified a previously unknown mechanism of cell death, termed "karyoptosis," observed in brain cells affected by Alzheimer's disease and frontotemporal dementia (FTD).
The research was conducted by scientists at King's College London, in collaboration with the UK Dementia Research Institute. The work was funded by Alzheimer's Research UK, the Biotechnology and Biological Sciences Research Council International Partnership, the UK Medical Research Council, and the UK Dementia Research Institute.
Methodology and Key Findings
The study analyzed 3,000 brain cells from 28 individuals diagnosed with either FTD or end-stage Alzheimer's disease.
The numbers are striking: 35% of cells from the frontal cortex of Alzheimer's patients showed signs of karyoptosis, compared to just 15% of cells from healthy aged controls.
Mechanism of Karyoptosis
According to the study, karyoptosis is a series of chemical reactions triggered by the accumulation of toxic proteins. This process destabilizes the nuclear envelope, causing the nucleus to shrink and disintegrate.
The researchers identified a specific interaction between the kinase p38 MAP kinase and the protein LaminB1 as a potential control point for this pathway.
Potential Therapeutic Implications
Experiments on rat neurons in vitro demonstrated that blocking the interaction between p38 MAP kinase and LaminB1 reduced markers associated with karyoptosis.
The researchers stated that this finding suggests a potential target for developing therapies aimed at slowing neuronal cell death in humans.
"Our study uncovers a new series of chemical events which can coordinate cell death in brain cells. We have started to lay out the road map of how karyoptosis works."
— Dr. Rebecca Casterton, UK Dementia Research Institute
"The identification of karyoptosis is a crucial step towards finding targets for treatments that could stop or slow cell loss."
— Dr. Sara Rodrigues, Alzheimer's Research UK