Scientists discover how Alzheimer's may destroy brain cells
Baku, July 15, AZERTAC
Scientists have identified a previously unrecognized form of cell death that appears to contribute to Alzheimer's disease and other neurodegenerative disorders, offering new insight into how brain cells are lost as these diseases progress. The findings suggest the newly described process, called karyoptosis, could become a potential target for future therapies, Qazinform News Agency reported.
The study, published in Nature Communications, examined how neurons respond to proteotoxic stress, a condition in which abnormal or misfolded proteins accumulate inside cells. Such protein buildup is a defining feature of Alzheimer's disease and several other forms of dementia. Researchers found that instead of dying through well-known mechanisms such as apoptosis, neurons can undergo a distinct process in which the nucleus progressively breaks down before the cell dies.
According to the researchers, karyoptosis begins when the cell's protein recycling system, known as the autophagy-lysosome pathway, becomes overwhelmed. This destabilizes the nuclear envelope, causing the nucleus to lose its structure, DNA damage to develop and nuclear material to be expelled from the cell. The team found that this process is driven by changes in a protein called Lamin B1, whose stability is regulated by the p38 MAP kinase signaling pathway.
The scientists tested the mechanism in multiple laboratory models, including cultured neurons, fruit flies and human neurons derived from stem cells. Blocking the p38 signaling pathway reduced damage to the nuclear envelope, improved neuron survival and lessened disease-related changes, suggesting the pathway plays a central role in triggering karyoptosis.
To determine whether the process also occurs in people, the researchers analyzed post-mortem brain tissue from patients with Alzheimer's disease and frontotemporal dementia. Using single-cell analysis, they identified hallmarks of karyoptosis in affected neurons and found these cells were significantly more common in diseased brains than in healthy age-matched controls. The authors estimate that this mechanism may account for an additional 18% to 20% of neuronal degeneration in Alzheimer's disease and frontotemporal dementia beyond that seen during normal aging.
The researchers say their findings reveal a previously unrecognized mechanism linking toxic protein accumulation to neuron loss. While more research is needed before the discovery can be translated into treatments, they believe targeting the molecular pathway behind karyoptosis could provide a new strategy for slowing neurodegeneration in Alzheimer's disease and related disorders.
Other news in this section
