San Francisco, CA – A recent study from researchers at the Chinese University of Hong Kong sheds light on the behavior of neurons in neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Lewy body dementia. By analyzing over 30,000 nuclei using advanced snRNA-seq techniques, the team discovered that neurons in these conditions tend to re-enter the cell cycle and quickly progress to senescence, showing signs of aging instead of completing the cycle to produce new cells.
The study, published in the open-access journal PLOS Biology, introduces a new bioinformatics tool that offers fresh insights into how neurons behave in diseased versus healthy brains. This finding could deepen our understanding of neurodegenerative diseases and pave the way for further research into the mechanisms underlying these conditions.
Most neurons in the brain are post-mitotic, meaning they have stopped dividing. However, a small proportion of neurons have been found to re-enter the cell cycle, leading to questions about their fate. The researchers utilized publicly accessible databases of snRNA-seq data to analyze the expression of cell cycle-related genes in individual neurons, revealing increased cell cycle re-entry in disease-affected brains.
Interestingly, the study found that neurons in the brains of Alzheimer’s disease patients re-entered the cell cycle at a higher rate compared to healthy brains. These neurons that re-entered the cycle and aged also showed increased expression of genes associated with a higher risk of Alzheimer’s disease. Similar trends were observed in patients with Parkinson’s disease and Lewy body dementia.
The researchers highlight the significance of this heightened re-entry of neurons in diseased brains, though the exact neurobiological implications are still unclear. The analytical approach used in this study may provide deeper insights into different neuronal subpopulations in the brain, shedding light on the mechanisms of neurodegenerative diseases.
Moving forward, the authors plan to conduct experimental validations of these findings in relevant human samples to further explore the role of these cells in brain aging and disease pathogenesis. The bioinformatics analytical pipeline developed in this study offers a new tool for dissecting cell cycle re-engaging and senescent neurons in healthy and diseased brains, presenting new opportunities for research in this field.