Breaking News: Neurons in Neurodegenerative Diseases Show Signs of Aging
Researchers have made a groundbreaking discovery about cells in neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Lewy body dementia. Neurons in these diseases, which tend to re-enter the cell cycle, face difficulties completing the cycle and instead exhibit signs of aging. The findings come from a study that utilized advanced snRNA-seq techniques, analyzing over 30,000 nuclei. This new understanding of neuron behavior brings fresh insights into the study of neurodegenerative diseases.
Key Facts
- Neurons that re-enter the cell cycle in neurodegenerative diseases, such as Alzheimer’s, often fail to produce new cells and instead progress towards senescence.
- Using snRNA-seq data, researchers studied the expression of approximately 350 cell cycle-related genes in individual neurons, revealing increased cell cycle re-entry in diseased brains.
- The study introduces a new bioinformatics approach that allows for the investigation of cell cycle re-entry and senescence in various conditions, shedding light on the potential link between neurodegeneration and cell cycle re-entry.
Neurons in Neurodegenerative Diseases More Vulnerable to Aging
Recent research published in the open-access journal PLOS Biology has uncovered a notable connection between neurodegenerative diseases and the re-entry of neurons into the cell cycle. This phenomenon, observed primarily in diseases like Alzheimer’s, Parkinson’s, and Lewy body dementia, has the potential to deepen our understanding of these debilitating conditions.
While most neurons in the brain stop dividing after reaching maturity, a small portion of neurons can recommit to the cell cycle. The fate of these re-entering neurons has remained poorly understood, prompting a study conducted by researchers at the Chinese University of Hong Kong.
The team utilized a sophisticated technique called “snRNA-seq” to analyze the RNA of more than 30,000 individual nuclei. By examining the expression of a set of cell cycle-related genes, researchers were able to determine the phase of the cell cycle in which each nucleus was located.
Excitingly, they discovered that a subset of excitatory neurons had re-entered the cell cycle. However, contrary to their expectations, these cells predominantly exhibited features of aging rather than producing new neurons. Specifically, the re-entering neurons displayed greater expression of genes associated with cellular senescence.
Notably, this study found a higher rate of cell cycle re-entry in neurons from the brains of Alzheimer’s disease patients. The re-entering neurons that underwent aging processes also displayed increased expression of genes linked to a higher risk of Alzheimer’s, including genes directly involved in the production of amyloid, a protein associated with the aggregation seen in the brains of Alzheimer’s patients.
Similar trends were observed in brains from patients with Parkinson’s disease and Lewy body dementia, showing an increased proportion of re-entering neurons compared to healthy brains.
While the full significance of heightened cell cycle re-entry in diseased brains remains unclear, this bioinformatics-based study opens new avenues for understanding neuronal subpopulations and disease mechanisms in neurodegenerative diseases. According to Kim Hai-Man Chow, the lead researcher from the Chinese University of Hong Kong, this analytical approach will provide new opportunities and vital insights for studying the role of these neurons in brain aging and disease progression.
About this Alzheimer’s Disease Research
Author: Claire Turner
Source: PLOS
Contact: Claire Turner – PLOS
Original Research: Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence by Kim Hai-Man Chow et al. PLOS Biology
Abstract:
Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence
Increasing evidence indicates that terminally differentiated neurons in the brain may recommit to a cell cycle-like process during neuronal aging and under disease conditions.
Because of the rare existence and random localization of these cells in the brain, their molecular profiles and disease-specific heterogeneities remain unclear.
Through a bioinformatics approach that allows integrated analyses of multiple single-nucleus transcriptome datasets from human brain samples, these rare cell populations were identified and selected for further characterization.
Our analyses indicated that these cell cycle-related events occur predominantly in excitatory neurons and that cellular senescence is likely their immediate terminal fate.
Quantitatively, the number of cell cycle re-engaging and senescent neurons decreased during the normal brain aging process, but in the context of late-onset Alzheimer’s disease (AD), these cells accumulate instead.
Transcriptomic profiling of these cells suggested that disease-specific differences were predominantly tied to the early stage of the senescence process, revealing that these cells presented more proinflammatory, metabolically deregulated, and pathology-associated signatures in disease-affected brains.
Similarly, these general features of cell cycle re-engaging neurons were also observed in a subpopulation of dopaminergic neurons identified in the Parkinson’s disease (PD)-Lewy body dementia (LBD) model.
An extended analysis conducted in a mouse model of brain aging further validated the ability of this bioinformatics approach to determine the robust relationship between the cell cycle and senescence processes in neurons in this cross-species setting.
