Scientists have found a new way that brain cells can die. They call it karyoptosis. This discovery may help us slow down Alzheimer’s disease and a condition called frontotemporal dementia (FTD).
Many brain diseases, such as ALS, Alzheimer’s, and FTD, have a common problem: bad proteins collect inside nerve cells. Over time these cells stop working and die, which leads to memory loss and other symptoms.
Researchers at King’s College London, together with the UK Dementia Research Institute, noticed that the known ways cells die did not fully explain the massive loss of neurons. They studied 3,000 brain cells from 28 people who had either FTD or late‑stage Alzheimer’s.
Using computer tools, they saw that about 35% of cells in the Alzheimer’s brains showed signs of karyoptosis, while only 15% of healthy older brains did.
Karyoptosis starts when toxic proteins build up inside a cell. The cell’s nucleus – the part that holds DNA – begins to shrink and eventually falls apart.
The team also found a molecular pathway that seems to control this process. When proteins clump together, they weaken the outer shell of the nucleus. This makes the nucleus collapse.
Scientists looked at special proteins called kinases, which act like switches. In lab tests with rat neurons, blocking these switches lowered the signs of karyoptosis. One switch, p38 MAP kinase, works together with another protein, LaminB1. This pair looks promising for future medicines.
“If we can stop p38 MAP kinase from teaming up with LaminB1, we might slow down cell death,” said Dr. Manolis Fanto, a researcher at King’s College London.
Understanding karyoptosis gives researchers a new roadmap. It could help create drugs that protect brain cells, giving other treatments more time to work.
The study, titled “Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress,” appeared in Nature Communications. Funding came from Alzheimer’s Research UK and several UK science agencies.