中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (4): 719-720.doi: 10.4103/1673-5374.382234

• 观点:退行性病与再生 • 上一篇    下一篇

与年龄相关的细胞环境变化与神经退行性疾病风险

  

  • 出版日期:2024-04-15 发布日期:2023-09-15

A perspective on age-related changes in cell environment and risk of neurodegenerative diseases

Alice Y. Liu*   

  1. Department of Cell Biology and Neuroscience, Rutgers State University of New Jersey, Piscataway, NJ, USA
  • Online:2024-04-15 Published:2023-09-15
  • Contact: Alice Y. Liu, PhD, liu@dls.rutgers.edu.

摘要: https://orcid.org/0000-0002-6984-1671 (Alice Y. Liu)

Abstract: “Age-related neurodegenerative disease” underscores human age as the primary risk factor for disease development: Alzheimer’s, Parkinson’s, and Huntington’s disease (HD) as examples. Reasons for the age-dependent delay in disease manifestation, in particular for autosomal dominant forms of the disease, and the underlying cause(s) of specific neuron dysfunction and death to manifest as memory loss, anxiety, depression, and agitation in disease subjects remain unclear. We are interested in understanding age-related changes in cell environment that can modulate the structure, function, aggregation, and pathogenicity of disease proteins implicated in neurodegenerative disease (ND), using the polyQ-expanded mutant Huntingtin protein (mHtt) that causes HD as a model for our studies. Our perspective is that age-related changes in cell milieu including a reduction in intracellular water content, increased crowding, and decreased macromolecular hydration can augment the innate propensities of disease proteins to structure, to engage in heterotypic binding to and quenching of key regulatory protein factors, to wreak havoc in cell signaling and regulation that drive disease pathogenesis, as well as to form disease protein aggregates through homotypic self-association. We are hopeful that a better understanding of age-related changes in cell milieu that are conducive to ND pathogenesis will contribute to efforts to delay or prevent neuron degeneration while supporting neuron survival and function for healthy aging. THEME: aging → decreased cell hydration and increased crowding → intrinsically disordered protein (IDP) structuring & aggregation → ND progression.