The Link Between Aging, Cellular Senescence, and Neurodegenerative Diseases
As we age, our risk of developing neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and ALS increases. The exact molecular mechanisms that connect aging, cellular senescence, and the onset of these brain disorders are still not fully understood. However, a recent study by researchers from Tokyo Medical and Dental University (TMDU) has shed light on the role of a nucleolar protein in this process.
Published in The EMBO Journal on August 5, 2024, the study led by Professor Hitoshi Okazawa focused on polyglutamine binding protein 3 (PQBP3), a protein that the team had discovered over 20 years ago. By examining the functions of various proteins in the PQBP family, the researchers honed in on PQBP3 and its role in cellular senescence.
Through super-resolution fluorescence microscopy, the team observed that PQBP3 relocates from the nucleolus to the nucleoplasm or cytoplasm during cellular senescence. This relocation was accompanied by the destabilization of the nuclear membrane, leading to the leakage of nuclear DNA into the cytoplasm. Further analysis revealed that PQBP3 binds to a protein called PSME3, which is involved in protein degradation and maintenance of the nuclear membrane.
In experiments conducted on cell cultures and mouse models of spinocerebellar ataxia type 1 (SCA1), the researchers found that PQBP3 levels decreased in the nucleolus, leading to destabilization of the cellular membrane. This discovery has significant implications for understanding the link between aging and neurodegenerative disorders.
Professor Okazawa believes that targeting PQBP3 could be a potential strategy for treating both aging-related neurodegeneration and cellular senescence. However, he also cautions that PQBP3’s role in regulating cellular pathology may have implications for cancer development.
Overall, this study provides valuable insights into the mechanisms underlying aging and neurodegenerative diseases. By unraveling this connection, researchers may be able to develop novel therapies for these debilitating conditions.
