中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (9): 1580-1589.doi: 10.4103/1673-5374.276320

• 综述:退行性病与再生 • 上一篇    下一篇

对肌萎缩侧索硬化Wnt信号转变的新见解:潜在的治疗靶点?

  

  • 出版日期:2020-09-08 发布日期:2020-09-23

New insights into Wnt signaling alterations in amyotrophic lateral sclerosis: a potential therapeutic target?

Carlos González-Fernández* , Pau González, Francisco Javier Rodríguez*   

  1. Laboratory of Molecular Neurology, Hospital Nacional de Parapléjicos (HNP), Toledo, Spain
  • Online:2020-09-08 Published:2020-09-23
  • Contact: Carlos González-Fernández, PhD, ccgf23@gmail.com; Francisco Javier Rodríguez, PhD, fjrodriguez@sescam.jccm.es.
  • Supported by:
    This work was supported by the Fondo de Investigación Sanitaria (FIS) of Instituto de Salud Carlos III (Grant number PI12/2895; FEDER co-funded).

摘要:

orcid:  0000-0002-3415-0723 (Carlos González-Fernández) 

           0000-0001-5902-7556 (Francisco Javier Rodríguez)

Abstract: Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by upper and lower motor neuron degeneration, which leads to progressive paralysis of skeletal muscles and, ultimately, respiratory failure between 2–5 years after symptom onset. Unfortunately, currently accepted treatments for amyotrophic lateral sclerosis are extremely scarce and only provide modest benefit. As a consequence, a great effort is being done by the scientific community in order to achieve a better understanding of the different molecular and cellular processes that influence the progression and/or outcome of this neuropathological condition and, therefore, unravel new potential targets for therapeutic intervention. Interestingly, a growing number of experimental evidences have recently shown that, besides its well-known physiological roles in the developing and adult central nervous system, the Wnt family of proteins is involved in different neuropathological conditions, including amyotrophic lateral sclerosis. These proteins are able to modulate, at least, three different signaling pathways, usually known as canonical (β-catenin dependent) and non-canonical (β-catenin independent) signaling pathways. In the present review, we aim to provide a general overview of the current knowledge that supports the relationship between the Wnt family of proteins and its associated signaling pathways and amyotrophic lateral sclerosis pathology, as well as their possible mechanisms of action. Altogether, the currently available knowledge suggests that Wnt signaling modulation might be a promising therapeutic approach to ameliorate the histopathological and functional deficits associated to amyotrophic lateral sclerosis , and thus improve the progression and outcome of this neuropathology

Key words: ALS, astrocytes, Frizzled, human, microglia, motor neuron, neurodegeneration, neuroinflammation, spinal cord, Wnt