中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (8): 1564-1565.doi: 10.4103/1673-5374.303020

• 观点:退行性病与再生 • 上一篇    下一篇

胰岛素样生长因子2治疗亨廷顿舞蹈病的潜力：通过控制蛋白稳定性减少错误折叠蛋白质负荷

  


  • 出版日期:2021-08-15 发布日期:2021-01-13

Therapeutic potential of insulin-like growth factor 2 in Huntington’s disease: controlling proteostasis to alleviate the load of misfolded protein

Paulina Troncoso-Escudero, Claudio Hetz*, Rene L. Vidal*   

  1. Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile (Troncoso-Escudero P, Hetz C, Vidal RL)
    Center for Geroscience, Brain Health and Metabolism, Santiago, Chile (Troncoso-Escudero P, Hetz C, Vidal RL) 
    Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile (Troncoso-Escudero P, Hetz C)
    Center for Integrative Biology, Faculty of Sciences, University Mayor, Chile (Troncoso-Escudero P, Vidal RL)
    Buck Institute for Research on Aging, Novato, CA, USA (Hetz C)
  • Online:2021-08-15 Published:2021-01-13
  • Contact: Claudio Hetz, PhD, chetz@uchile.cl; Rene L. Vidal, PhD, rene.vidal@umayor.cl.
  • Supported by:
    This work was supported by Agencia Nacional de Investigación y Desarrollo (ANID) and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP), No. 15150012 (to CH and RLV); Millennium Institute, No. P09-015-F (to CH and RLV); Fondo de fomento al desarrollo científico (FONDEF), No. ID16I10223, D11E1007 (to CH); Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT), No. 1180186 (to CH) and 1191003 (to RLV); U.S. Air Force Office of Scientific Research 20RT0419; Michael J Fox For Parkinson’s Research Target Validation ID 12473.01 (to CH) and Consejo Nacional de Ciencia y tecnología (CONICYT), No. 21160843 (to PTE).

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摘要： https://orcid.org/0000-0001-7724-1767 
(Claudio Hetz);
https://orcid.org/0000-0002-4305-7387 
(Rene L. Vidal)

Abstract: Huntington’s disease (HD) is an inherited autosomal dominant neurodegenerative disorder characterized by the development of adult-onset motor dysfunction, psychiatric disturbances and intellectual decline. HD is associated with an expansion of CAG repeat sequence in the huntingtin gene (Htt). Exon 1 of Htt normally contains between 6 to 35 CAG repeats, whereas in patients affected with HD it contains more than 40 trinucleotides. The mutant Htt protein (mHtt) exhibits gain-of-toxic properties that cause neuronal dysfunction and death (Saudou and Humbert, 2016). Protein misfolding and aggregation is a common molecular feature of HD, suggesting that impairment in the buffer capacity of the proteostasis network contributes to the pathogenesis of the disease. Multiple studies in cell culture and animal models, in addition to the analysis of postmortem human tissue, have indicated that one of the main nodes of the proteostasis network affected in HD involves the function of the endoplasmic reticulum (Vidal et al., 2011). XBP1 is a master regulator of the unfolded protein response (UPR), the main adaptive pathway to cope with endoplasmic reticulum stress (Hetz et al., 2020). We previously reported that the genetic disruption of the transcription factor XBP1 delays disease progression and reduces protein aggregation in models of HD (Vidal et al., 2012), in addition to amyotrophic lateral sclerosis (ALS; Hetz et al., 2009), Parkinson´s disease (Valdes et al., 2014) and Alzheimer´s disease (Duran-Aniotz et al., 2017).