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

作     者：Carlos González-Fernández Pau González Francisco Javier Rodríguez Carlos González-Fernández;Pau González;Francisco Javier Rodríguez

作者机构：Laboratory of Molecular Neurology Hospital Nacional de Parapléjicos (HNP) 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2020年第15卷第9期

页      面：1580-1589页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the Fondo de Investigación Sanitaria(FIS)of Instituto de Salud Carlos III(Grant number PI12/2895 FEDER co-funded) 

主　　题：ALS astrocytes Frizzled human microglia motor neuron neurodegeneration neuroinflammation spinal cord Wnt 

摘      要：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 neuropathologica 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.