中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (2): 393-394.doi: 10.4103/1673-5374.377608

• 观点:退行性病与再生 • 上一篇    下一篇

通过人工实施未折叠蛋白反应来预防大脑老化:未来方向

  

  • 出版日期:2024-02-15 发布日期:2023-08-30

Preventing brain aging by the artificial enforcement of the unfolded protein response: future directions

Felipe Cabral-Miranda, Claudio Hetz*   

  1. Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (Cabral-Miranda F)
    Center for Geroscience, Brain Health and Metabolism, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA, USA (Hetz C)
  • Online:2024-02-15 Published:2023-08-30
  • Contact: Claudio Hetz, PhD, chetz@uchile.cl or chetz@buckinstitute.org.
  • Supported by:
    This work was funded by U.S. Air Force Office of Scientific Research, No. FA9550-21-1-0096, FONDAP program, No. 15150012, Department of Defense grant, Nos. W81XWH2110960, ANID/FONDEF ID1ID22I10120, and ANID/NAM22I0057 and Swiss Consolidation Grant -The Leading House for the Latin American Region (all to CH).

摘要: https://orcid.org/0000-0003-1120-7966 (Claudio Hetz)

Abstract: As the life expectancy of the world’s population increases, age-related diseases are emerging as one of the greatest problems facing modern society. The onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families. The field of aging has defined a number of interrelated pathways and cellular processes, commonly referred to as the “hallmarks of aging,” some of which have emerged as causal factors for age-related changes in brain function (López-Otín et al., 2013). Since most neurodegenerative diseases are characterized by the abnormal deposition of protein aggregates, the deregulation of proteostasis, one of the central pillars of aging, may represent one of the molecular links between normal aging and brain diseases. Indeed, a reduction in the buffering capacity of the proteostasis network is observed during normal aging in various tissues, including the brain, a phenomenon that is exacerbated in neurodegenerative diseases. One of the major nodes of the proteostasis network affected during aging in different species (humans, mice, flies, worms, and yeast) involves the function of the endoplasmic reticulum (ER) and the unfolded protein response (UPR), a signaling pathway that is activated following ER stress (Taylor and Hetz, 2020).