中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (8): 1655-1657.doi: 10.4103/1673-5374.389644

• 观点:退行性病与再生 • 上一篇    下一篇

成熟TAU亚型的抑制可预防阿尔茨海默病样淀粉样蛋白β低聚物诱导的啮齿类神经元棘突缺失

  

  • 出版日期:2024-08-15 发布日期:2024-01-03

Suppression of mature TAU isoforms prevents Alzheimer’s disease-like amyloid-beta oligomer-induced spine loss in rodent neurons

Sarah Buchholz#, Hans Zempel*, #   

  1. Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (Buchholz S, Zempel H) 
    Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany (Buchholz S, Zempel H)
  • Online:2024-08-15 Published:2024-01-03
  • Contact: Hans Zempel, PhD, MD,hans.zempel@uk-koeln.de.
  • Supported by:
    This work was supported by the Deutsche Forschungsgemeinschaft and the Else-Kröner-Fresenius-Stiftung (to HZ).

摘要: https://orcid.org/0000-0002-7510-3077 (Hans Zempel)

Abstract: Introduction: TAU isoforms as disease mediators: The microtubule-associated protein TAU is predominantly present in the axons of neurons under physiological conditions. In Alzheimer’s disease (AD) and related tauopathies, TAU also mislocalizes (“TAU missorting”) to the soma and the dendrites, where it eventually forms aggregates, the so-called neurofibrillary tangles (for review see Zimmer-Bensch and Zempel, 2021; Zempel, 2023). Alternative splicing of the TAU encoding MAPT gene results in eight major TAU isoforms, six of which are expressed in the human brain, while only three are present in the adult rodent brain (Goedert et al., 1989; Bullmann et al., 2009). The axodendritic distribution of the different TAU isoforms is strikingly different in neurons. The longest and least expressed (< 10% of the whole TAUom in the human central nervous system (CNS)) isoform of TAU, 2N4R-TAU, e.g., is partially retained in the somatodendritic compartment, where it induces enhanced dendritic outgrowth and spine maturation (Zempel et al., 2017; Bachmann et al., 2021). Amyloid-beta oligomers (AβO) induce pathological TAU missorting and the loss of dendritic spines, a sensitive measure of synaptic health and function. Interestingly, TAU depletion in mice, primary rodent neurons, and induced pluripotent stem cell (iPSC)-derived human neurons protects them from AβO toxicity, spine loss, and consequential neuronal dysfunction (Roberson et al., 2007; Zempel et al., 2013; Buchholz et al., 2022).