In a recent study published in PLOS Biology by Kim Hai-Man Chow and colleagues from the Chinese University of Hong Kong, it was revealed that neurons in the brain which re-enter the cell cycle after mitosis are prone to quick senescence, a process commonly associated with Alzheimer’s disease. This sheds light on the mechanism of neurodegeneration. The study's methodology could also be applied to investigate other cell types in the brain.
Traditionally, it was believed that most neurons in the brain stop dividing after entering the mitotic phase, with little information available about those that do not conform to this pattern.
The researchers utilized snRNA-seq, a database for single nuclei RNA sequencing, to isolate and analyze neuronal cell cycle re-engagement. They used a bioinformatics pipeline to identify the molecular profiles associated with this phenomenon. The data encompassed over 30,000 nuclei, each evaluated for the expression of approximately 350 cell cycle-related genes.
The results indicated that certain groups of excitatory neurons had re-entered the cell cycle but failed to progress through it to generate daughter neurons. Instead, these re-entry cells exhibited gene expression patterns associated with senescence, regaining the ability to enter senescence.
The study's findings were significant, revealing a higher rate of cell cycle re-entry in neurons from Alzheimer's disease patients. Furthermore, these re-entering neurons displayed elevated expression of genes linked to Alzheimer's disease, including those involved in amyloid formation. Similarly, brains afflicted with Parkinson's disease and Lewy body dementia exhibited a greater proportion of re-entering neurons compared to healthy brains.
In summary, this research uncovers a previously overlooked aspect of neuronal behaviour in neurodegenerative diseases, highlighting the potential role of cell cycle re-entry in the pathogenesis of Alzheimer's, Parkinson's, and Lewy body dementia.
