New research shows that post-mitotic neurons in the brain, especially in Alzheimer’s patients, can re-enter the cell cycle and become senescent, potentially offering insights into neurodegeneration and a new method for studying brain diseases.
This uncommon process is more frequently observed in neurodegenerative diseases and could offer insights into disease mechanisms.
According to a new study published in PLOS Biology by Kim Hai-Man Chow and colleagues from the Chinese University of Hong Kong, neurons in the brain that re-enter the cell cycle after mitosis are prone to quick senescence, a process observed more frequently in
Summary image of the article. The upper part highlights neuronal cell cycle re-engagement is a stage proceeding neuronal senescence and that their full molecular profiles can now be identified by the bioinformatics pipeline we reported in the accepted manuscript. The bottom part is a simplified version of Figure 1A from the paper. The upper panel is created by the BioRender application. Credit: Kim Hei-Man Chow (CC-BY 4.0)
To address this question, the authors turned to publicly accessible databases of “snRNA-seq” data, in which individual single nuclei are isolated and their Related Post Colorful foods could enhance athletes' vision
RNA
Ribonucleic acid (RNA) is a polymeric molecule similar to DNA that is essential in various biological roles in coding, decoding, regulation and expression of genes. Both are nucleic acids, but unlike DNA, RNA is single-stranded. An RNA strand has a backbone made of alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four bases—adenine (A), uracil (U), cytosine (C), or guanine (G). Different types of RNA exist in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).
” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>RNA is sequenced, providing a snapshot of what a cell was doing at the time of isolation. The cell cycle proceeds through distinct phases, including growth, Related Post This Ancient Organism Crawled Onto Land Over 400 Million Years Ago : ScienceAlert
Their data included information on over 30,000 nuclei, each of which was assigned a score based on the level of expression of a set of about 350 cell cycle-related genes. They found that small populations of excitatory neurons had indeed re-entered the cell cycle. These cells did not, for the most part, continue successfully through the cell cycle to produce daughter neurons, however. Instead, cells undergoing re-entry also had elevated expression of genes associated with senescence; in effect, the cells had reawakened only to enter senescence.
Implications for Neurodegenerative Diseases
Intriguingly, the authors found that neurons in the brains of Alzheimer’s disease patients reentered the cell cycle at a higher rate, and that those neurons that had reentered the cell cycle and aged had increased expression of multiple genes associated with a higher risk of Alzheimer’s disease, including those that contribute directly to the production of amyloid, the sticky protein that aggregates in the AD brain. Similarly, brains from patients with Parkinson’s disease and Lewy body dementia had an increase in the proportion of re-entering neurons compared to healthy brains.
The neurobiological significance of this heightened re-entry for the diseased brain is still unclear, but the analytical approach taken here may offer deeper insights into neuronal subpopulations within the brain, as well as shedding light on disease mechanisms in neurodegenerative diseases.
“Because of the rare existence and random localization of these cells in the brain, their molecular profiles and disease-specific heterogeneities remain unclear,” Chow said. “While experimental validations of these findings in relevant human samples will be conducted in the future, the applicability of this analytical approach in different diseases and cross-Related Post Planet images of the Lake Kivu landslides in the DRC - The Landslide Blog
species
A species is a group of living organisms that share a set of common characteristics and are able to breed and produce fertile offspring. The concept of a species is important in biology as it is used to classify and organize the diversity of life. There are different ways to define a species, but the most widely accepted one is the biological species concept, which defines a species as a group of organisms that can interbreed and produce viable offspring in nature. This definition is widely used in evolutionary biology and ecology to identify and classify living organisms.
” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>species settings offers new opportunities and insights to supplement mainstay histological-based approaches in studying the roles of these cells in brain aging and disease pathogenesis.”
The authors add, “This bioinformatics analytical pipeline demonstrated will offer the field a new tool to unbiasedly dissect cell cycle re-engaging and senescent neurons, and to dissect their heterogeneities in healthy versus disease-affected brains.”
Reference: “Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence” by Deng Wu, Jacquelyne Ka-Li Sun and Kim Hei-Man Chow, 23 April 2024, PLOS Biology.
DOI: 10.1371/journal.pbio.3002559
The work was supported, in part, by grants from the following: The Hong Kong Research Grants Council (RGC)-General Research Fund (GRF) (PI: ECS24107121, GRF16100219 and GRF16100718) (all to K.H-M.C) and the RGC- Collaborative Research Fund (CRF) (Co-I: C4033-19EF) (K.H-M.C); the National NaturalScience Foundation-Excellent Young Scientists Fund 2020 (Ref: 32022087) (K.H-M.C); Alzheimer’s Association Research Fellowship (PI: AARF-17-531566) (K.H-M.C).